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DRUG:

Provenge (sipuleucel-T)

i
Other names: APC8015, autologous PAP-loaded dendritic cell vaccine, APC 8015, APC-8015, APC8015F, APC-8015F, APC 8015F
Company:
Bausch Health
Drug class:
Immunostimulant, Prostatic acid phosphatase inhibitor
Related drugs:
1m
Trial completion
|
Provenge (sipuleucel-T)
2ms
Peripheral blood interferon responses to toll-like receptor 1/2 signaling associate with longer survival in men with metastatic prostate cancer treated with Sipleucel-T. (PubMed, Cancer Res Commun)
IFN-β responses to TLR1/2 signaling correlated with increased numbers of IFN-β producing T cells after broad, tumor antigen independent stimulation. Thus, peripheral innate immunity differs by race, may predict survival after sip-T, and associates with peripheral T cell functionality in men with mCRPC.
Journal • IO biomarker • Metastases
|
IFNB1 (Interferon Beta 1)
|
Provenge (sipuleucel-T)
3ms
Study of Sipuleucel-T With or Without Continuing New Hormonal Agents in Metastatic Prostate Cancer (clinicaltrials.gov)
P2, N=26, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Oct 2025 --> Oct 2024
Trial primary completion date • Metastases
|
Xtandi (enzalutamide capsule) • abiraterone acetate • Erleada (apalutamide) • Provenge (sipuleucel-T)
5ms
OU-SCC-EXCITE: Sipuleucel-T Based Autologous Cellular Immunotherapy for Advanced Prostate Cancer (clinicaltrials.gov)
P1, N=12, Recruiting, University of Oklahoma | Trial completion date: May 2024 --> Nov 2024 | Trial primary completion date: May 2024 --> Nov 2024
Trial completion date • Trial primary completion date • Metastases
|
Provenge (sipuleucel-T)
5ms
Race-related Differences in Sipuleucel-T Response Among Men with Metastatic Castrate-Resistant Prostate Cancer. (PubMed, Cancer Res Commun)
The data suggest that immune correlates in blood differ in AA and non-AA with mCRPC pre- and post-sipuleucel-T.
Journal • IO biomarker • Metastases
|
CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • ICAM1 (Intercellular adhesion molecule 1) • ICOS (Inducible T Cell Costimulator) • PSAP (Prostatic Acid Phosphatase)
|
Provenge (sipuleucel-T)
6ms
The role of immunotherapy in urological cancers. (PubMed, Arch Ital Urol Androl)
Immunotherapeutic agents used in urothelial carcinoma include various options such as BCG, interferon, anti-PD-1 (pembrolizumab, nivolumab) and anti-PD-L1 (atezolizumab, avelumab, durvalumab)...In light of randomized clinical trials conducted with increasing interest in the application of immunotherapies in the adjuvant setting, combination therapies (nivolumab/ipilimumab, nivolumab/cabozantinib, pembrolizumab/ axitinib, pembrolizumab/lenvantinib) have become the standard first-line treatment of metastatic RCC...Ipilimumab, nivolumab, pembrolizumab, atezolizumab, and Sipuleucel T (Vaccine-based) are promising alternative treatment options. Considering ongoing randomized clinical trials, immunotherapeutic agents promise to transform the uro-oncology field significantly. In this review, we aimed to summarize the role of immunotherapy in urothelial, renal and prostate cancer in the light of randomized clinical trials.
Clinical • Journal
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CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)
|
Keytruda (pembrolizumab) • Opdivo (nivolumab) • Tecentriq (atezolizumab) • Yervoy (ipilimumab) • Imfinzi (durvalumab) • Lenvima (lenvatinib) • Bavencio (avelumab) • Cabometyx (cabozantinib tablet) • Inlyta (axitinib) • Provenge (sipuleucel-T)
9ms
OU-SCC-EXCITE: Sipuleucel-T Based Autologous Cellular Immunotherapy for Advanced Prostate Cancer (clinicaltrials.gov)
P1, N=12, Recruiting, University of Oklahoma | Trial completion date: Feb 2024 --> May 2024 | Trial primary completion date: Feb 2024 --> May 2024
Trial completion date • Trial primary completion date • Metastases
|
Provenge (sipuleucel-T)
9ms
High dimensional analyses reveal IL-15 enhances activation of Sipuleucel-T lymphocyte subsets and reverses immunoresistance. (PubMed, Cancer Immunol Res)
Evaluation of tumor-infiltrating lymphocytes revealed a 2-14-fold higher influx of sip-T and a significant increase in IFN-γ producing CD8+ T cells and NKT cells within the tumor microenvironment (TME) in the IL-15 group. In conclusion, we put forward evidence that IL-15 treatment can enhance the functional antitumor immunity of sip-T, providing rationale for combining IL-15 or IL-15 agonists with sip-T to treat patients with mCRPC.
Journal
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • IL15 (Interleukin 15)
|
Provenge (sipuleucel-T)
10ms
Sipuleucel-T Combined With Bipolar Androgen Therapy in Men With mCRPC (clinicaltrials.gov)
P2, N=26, Recruiting, Yale University | Not yet recruiting --> Recruiting
Enrollment open • Metastases
|
Provenge (sipuleucel-T)
11ms
OU-SCC-EXCITE: Sipuleucel-T Based Autologous Cellular Immunotherapy for Advanced Prostate Cancer (clinicaltrials.gov)
P1, N=12, Recruiting, University of Oklahoma | Trial completion date: Jul 2027 --> Feb 2024 | Trial primary completion date: May 2024 --> Feb 2024
Trial completion date • Trial primary completion date • Metastases
|
Provenge (sipuleucel-T)
11ms
Real-world utilization patterns of radium-223 in metastatic prostate cancer in the United States: An administrative claims database study. (ASCO-GU 2024)
Therapies received prior to Ra-223 were androgen receptor pathway inhibitors (75.4%), chemotherapy (32.1%), sipuleucel-T (13.7%) and bone health agents (73.7%). Ra-223 was utilized as a combination therapy by 26.0% of the overall population, predominately with enzalutamide... Nearly half of men completed 5+ cycles of Ra-223 therapy in a large US cohort of relatively young mCRPC men with private health insurance. Advanced disease state with short survival and low comorbidity were key factors associated with lower completion of 5+ cycles. The findings highlight the importance of utilizing Ra-223 early after mCRPC diagnosis, when the probability of >6-month survival is higher, to enhance treatment completion that has been shown to result in better outcomes.
Clinical • Real-world evidence • Claims database • Real-world • Metastases
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Xtandi (enzalutamide capsule) • Xofigo (radium Ra-223 dichloride) • Provenge (sipuleucel-T)
11ms
Effect of combined treatment with sipuleucel-T and IL-15 on tumor control, tumor-infiltrating immune effectors, and key mediators of immunoresistance in a preclinical prostate cancer model. (ASCO-GU 2024)
This is the first study to evaluate the sip-T product using CyTOF, and the first pre-clinical in vivo prostate tumor modeling of sip-T. IL-15 treatment significantly enhances anti-tumor efficacy, effector immune cell activation and tumor infiltration, and reverses key mediators of immune suppression. Studies with modified IL-15 cytokines are ongoing and will be presented.
Preclinical • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CD276 (CD276 Molecule) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • IL15 (Interleukin 15)
|
Provenge (sipuleucel-T)
12ms
Sipuleucel-T Based Autologous Cellular Immunotherapy for Advanced Prostate Cancer (clinicaltrials.gov)
P1, N=12, Recruiting, University of Oklahoma | Not yet recruiting --> Recruiting | Initiation date: Oct 2023 --> Jan 2024
Enrollment open • Trial initiation date • Metastases
|
Provenge (sipuleucel-T)
12ms
Activation of Dendritic Cells Isolated from the Blood of Patients with Prostate Cancer by Ex Vivo Fluid Shear Stress Stimulation. (PubMed, Curr Protoc)
Provenge (sipuleucel-T) is an autologous cancer-vaccine-based immunotherapy approved for men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC)...Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Sample collection and DC isolation Basic Protocol 2: Determination and application of fluid shear stress Basic Protocol 3: Flow cytometry analysis of DCs after FSS stimulation.
Preclinical • Journal
|
CSF2 (Colony stimulating factor 2) • PSAP (Prostatic Acid Phosphatase)
|
Provenge (sipuleucel-T)
1year
New P3 trial • Metastases
|
Provenge (sipuleucel-T)
1year
New P2 trial • Metastases
|
PSAP (Prostatic Acid Phosphatase)
|
Provenge (sipuleucel-T)
1year
ProVent: Open- Label Trial of Sipuleucel-T Administered to Active Surveillance Patients for Newly Diagnosed Prostate Cancer (clinicaltrials.gov)
P3, N=450, Active, not recruiting, Dendreon | Trial completion date: May 2023 --> Feb 2024 | Trial primary completion date: May 2023 --> Dec 2023
Trial completion date • Trial primary completion date
|
Provenge (sipuleucel-T)
1year
A review of strategies to overcome immune resistance in the treatment of advanced prostate cancer. (PubMed, Cancer Drug Resist)
Since regulatory approval of the vaccine therapy sipuleucel-T in the biomarker-unselected population, there has not been much success with immunotherapy treatment in advanced prostate cancer...On the horizon, novel drugs using bispecific T-cell engager (BiTE) and chimeric antigen receptors (CAR) technology are being explored and have shown promising early efficacy in this disease. Here we discuss the features of the tumour microenvironment that predispose to immune resistance and rational strategies to enhance antitumour responsiveness in advanced prostate cancer.
Review • Journal • IO biomarker • Metastases
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AR (Androgen receptor) • CDK12 (Cyclin dependent kinase 12)
|
MSI-H/dMMR • AR splice variant 7
|
Provenge (sipuleucel-T)
over1year
Combination Treatment with Sipuleucel-T and Abiraterone Acetate or Enzalutamide for Metastatic Castration-Resistant Prostate Cancer: STAMP and STRIDE Trials. (PubMed, Clin Cancer Res)
Median OS was consistent regardless of whether the agents were administered sequentially or concurrently, including after NDI update. Results suggest that sipuleucel-T induces an immunologic prime-boost effect after initial sipuleucel-T exposure, even when combined with ARTAs.
Journal • Metastases
|
AR (Androgen receptor) • PSAP (Prostatic Acid Phosphatase)
|
Xtandi (enzalutamide capsule) • abiraterone acetate • Provenge (sipuleucel-T)
over1year
MODULE 3: Available and Emerging Strategies for Newly Diagnosed Metastatic CRPC (mCRPC) (ASCO 2023)
This activity is supported by educational grants from AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, Lilly, Merck, and Sanofi. Key clinical and biological factors in the selection of therapy for newly diagnosed mCRPC; influence of earlier use of secondary hormonal therapy and chemotherapy on current management approaches Key findings from clinical trial and real-world data sets exploring the efficacy and safety of sipuleucel-T Optimal patient selection for treatment with sipuleucel-T; importance of early identification of appropriate candidates Data sets defining the role of secondary hormonal therapies for patients with mCRPC, including those who have received one of these agents in an earlier disease setting Role of the CDK4/6 pathway in prostate cancer proliferation and resistance to androgen receptor (AR)-targeted therapy Available efficacy and safety findings with CDK4/6 inhibitors for mCRPC Design, eligibility criteria and primary and secondary endpoints of the Phase II/III CYCLONE 2 trial evaluating first-line abiraterone and prednisone with or without abemaciclib for mCRPC
Metastases
|
Verzenio (abemaciclib) • abiraterone acetate • prednisone • Provenge (sipuleucel-T)
over1year
Emerging treatment options for prostate cancer. (PubMed, Expert Rev Anticancer Ther)
Treatment landscape for metastatic castrate-resistant prostate cancer (mCRPC) has evolved beyond additional agents with ARPI and/or docetaxel, including other treatments with sipuleucel-T, radium, cabazitaxel, PARP inhibitors, and lutetium, which have specific indications and role in sequencing. Novel therapies remain critically needed after progression from lutetium.
Journal
|
docetaxel • cabazitaxel • Provenge (sipuleucel-T)
over1year
Comparative real-world (RW) evidence on darolutamide (Daro), enzalutamide (Enza), and apalutamide (Apa) for patients (Pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) in the United States: DEAR. (ASCO 2023)
Sponsored by Pharmaceutical/Biotech Company, Bayer AG. Overall, a lower % of pts discontinued initial ARI treatment, progressed to metastasis, or had AEs on daro vs enza/apa. In analyses adjusting for observed BL factors, pts on daro had considerably lower risk of DISC and PROG vs enza/apa. This study confirms daro’s strong efficacy and favorable tolerability profile in a RW setting.
Real-world evidence • Clinical • Real-world • Metastases
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docetaxel • Xtandi (enzalutamide capsule) • abiraterone acetate • mitoxantrone • Nubeqa (darolutamide) • cabazitaxel • Erleada (apalutamide) • Xofigo (radium Ra-223 dichloride) • Provenge (sipuleucel-T)
over1year
Avelumab in Men With Metastatic Castration-Resistant Prostate Cancer, Enriched for Patients Treated Previously With a Therapeutic Cancer Vaccine. (PubMed, J Immunother)
Therapeutic cancer vaccines including sipuleucel- T , a prostatic acid phosphatase (PAP) targeted vaccine that improves survival in metastatic castration-resistant prostate cancer (mCRPC), can produce immune responses that translate to clinical benefit...Eighteen patients enrolled, and previous treatments included abiraterone or enzalutamide in 14 (78%), therapeutic cancer vaccine in 14 (78%), and chemotherapy in 4 (22%)...Analysis of antigen-specific T-cell responses pre and postavelumab treatment did not demonstrate changes in interferon-γ production or proliferation in response to PAP or PA2024. This unplanned analysis does not support the use of sequential therapeutic cancer vaccine therapy followed by programmed death ligand-1 inhibition in mCRPC.
Journal • Metastases
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IFNG (Interferon, gamma) • PSAP (Prostatic Acid Phosphatase)
|
Bavencio (avelumab) • Xtandi (enzalutamide capsule) • abiraterone acetate • Provenge (sipuleucel-T)
over1year
Prostate cancer and novel pharmacological treatment options - what's new for 2022? (PubMed, Expert Rev Clin Pharmacol)
Androgen deprivation therapy (ADT) plus Androgen Receptor Target Agents (ARTAs) or docetaxel are the actual standard of care in prostate cancer (PC). Several therapeutic options are available for pretreated patients: cabazitaxel, olaparib, and rucaparib for BRCA mutations, Radium-223 for selected patients with symptomatic bone metastasis, sipuleucel T, and 177 LuPSMA-617...The radionuclide Lu-PSMA-617 proved successful outcomes in pretreated mCRPC patients. Additional studies will better clarify the appropriate candidates to each strategy and the correct treatments' sequence.
Journal • BRCA Biomarker • PARP Biomarker • IO biomarker
|
AR (Androgen receptor) • BRCA (Breast cancer early onset)
|
BRCA mutation
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Lynparza (olaparib) • docetaxel • Rubraca (rucaparib) • cabazitaxel • Pluvicto (lutetium Lu 177 vipivotide tetraxetan) • Xofigo (radium Ra-223 dichloride) • Provenge (sipuleucel-T)
almost2years
Systemic Therapies for Metastatic Castration-Resistant Prostate Cancer: An Updated Review. (PubMed, World J Mens Health)
In the past decade, new treatment options for mCRPC, including abiraterone, enzalutamide, docetaxel, cabazitaxel, sipuleucel-T, radium-223, Lu-PSMA-617, and Olaparib, have demonstrated a survival benefit in phase 3 trials. Bone-modifying agents have become part of the overall treatment strategy for mCRPC, in which denosumab and zoledronic acid reduce skeletal-related events...Tumors with gene alterations that affect homologous recombination repair, such as BRCA1 and BRCA2 alterations, are sensitive to poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors in mCRPC. This review sought to highlight recent advances in systemic therapy for mCRPC and strategies to support patient selection and treatment sequencing.
Review • Journal • BRCA Biomarker • PARP Biomarker • Metastases
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
|
BRCA2 mutation • FOLH1 positive
|
Lynparza (olaparib) • docetaxel • Xtandi (enzalutamide capsule) • abiraterone acetate • Prolia (denosumab) • cabazitaxel • zoledronic acid • Pluvicto (lutetium Lu 177 vipivotide tetraxetan) • Xofigo (radium Ra-223 dichloride) • Provenge (sipuleucel-T)
almost2years
MODULE 3: Current Therapeutic Options for Patients with Newly Diagnosed Metastatic Castration-Resistant Prostate Cancer (mCRPC) (ASCO-GU 2023)
CME Provider and Supporter(s): This event is organized and accredited by Research to Practice and supported through educational grants provided by Astellas and Pfizer Inc, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Exelixis Inc, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, Lilly, Merck, and Sanofi. Key clinical and biologic factors in the selection of therapy for patients with newly diagnosed mCRPC; impact of earlier use of secondary hormonal therapy and chemotherapy on current disease management approaches Key findings from clinical trial and real-world data sets exploring the efficacy and safety of sipuleucel-T; impact of patient age, race, PSA level and other factors on outcomes Optimal patient selection for sipuleucel-T; importance of early identification of candidates Biologic basis for combining PARP inhibitors with antiandrogen therapies for prostate cancer; rationale for the potential activity of these combinations in patients without homologous recombination repair (HRR) gene mutations Available and emerging data (eg, from the PROpel, MAGNITUDE and TALAPRO-2 trials) with PARP inhibitors combined with secondary hormonal agents for previously untreated mCRPC Rationale for the evaluation of CDK4/6 inhibitors among patients with mCRPC Design, eligibility criteria and primary and secondary endpoints of the Phase II/III CYCLONE 2 trial evaluating first-line abiraterone and prednisone with or without abemaciclib for mCRPC; estimated completion date
Clinical • PARP Biomarker • Metastases
|
HRD (Homologous Recombination Deficiency)
|
Verzenio (abemaciclib) • abiraterone acetate • Provenge (sipuleucel-T)
2years
REAL-WORLD PREVALENCE OF SELECT HOMOLOGOUS RECOMBINATION REPAIR (HRR) ALTERATIONS IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC) (SUO 2022)
Most common 1L treatments included enzalutamide (30.7%), abiraterone acetate (29.9%), docetaxel (19.7%), sipuleucel-T (8.9%), and radium-223 (5.2%). HRR alterations were identified in about 1 in 5 tested patients initiating mCRPC treatment. Future studies should focus on understanding alteration testing strategies in diverse clinical practice settings to ensure patients with HRR alterations are identified in a timely manner and receive appropriate clinical management.
Clinical • Real-world evidence • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • HDAC2 (Histone deacetylase 2)
|
BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • FANCA mutation
|
docetaxel • Xtandi (enzalutamide capsule) • abiraterone acetate • Xofigo (radium Ra-223 dichloride) • Provenge (sipuleucel-T)
2years
Safety and efficacy of avelumab plus carboplatin in patients with metastatic castration-resistant prostate cancer in an open-label Phase Ib study. (PubMed, Br J Cancer)
Avelumab plus carboplatin has an acceptable safety profile and was associated with a prolonged OS given the heavily pretreated population.
P1 data • Journal • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
|
BRCA2 (Breast cancer 2, early onset)
|
Yervoy (ipilimumab) • carboplatin • Bavencio (avelumab) • Provenge (sipuleucel-T)
2years
Signaling new therapeutic opportunities: cytokines in prostate cancer. (PubMed, Expert Opin Biol Ther)
Despite FDA approval of sipuleucel-T in 2010, endeavors to use immune checkpoint inhibitors in unselected prostate cancer patients have not improved clinical outcomes...Cytokine-based therapies present an alternative immune strategy to target the pleiotropic prostate cancer tumor microenvironment beyond T-cells. Future immunotherapy strategies in prostate cancer should address these immune cell populations which may play more important roles in the prostate cancer tumor microenvironment.
Journal
|
CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL23A (Interleukin 23 Subunit Alpha) • IL15 (Interleukin 15)
|
Provenge (sipuleucel-T)
2years
Genetic engineering of baculovirus-insect cell system to improve protein production. (PubMed, Front Bioeng Biotechnol)
To date, eleven BEVS-derived products have been approved for use, including four human vaccines [Cervarix against cervical cancer caused by human papillomavirus (HPV), Flublok and Flublok Quadrivalent against seasonal influenza, Nuvaxovid/Covovax against COVID-19], two human therapeutics [Provenge against prostate cancer and Glybera against hereditary lipoprotein lipase deficiency (LPLD)] and five veterinary vaccines (Porcilis Pesti, BAYOVAC CSF E2, Circumvent PCV, Ingelvac CircoFLEX and Porcilis PCV). As the demand for biotechnology increases, there has been a concomitant effort into optimizing yield, stability and protein glycosylation through genetic engineering and the manipulation of baculovirus vector and host cells. In this review, we summarize the strategies and technological advances of BEVS in recent years and explore how this will be used to inform the further development and application of this system.
Review • Journal
|
LPL (Lipoprotein Lipase)
|
Provenge (sipuleucel-T) • Cervarix (recombinant human papillomavirus bivalent vaccine)
2years
IL-15 enhances cytotoxicity of sipuleucel-T from metastatic castration-resistant prostate cancer patients by activating CD8+ T and NK effector cells (SITC 2022)
Conclusions This is the first comprehensive study to evaluate the composition of sip-T from mCRPC patients using high dimensional CyTOF analysis, and serves as an important reference source for further modification and improvement of sip-T efficacy. Furthermore, our data is the first to show that the addition of IL-15 to sip-T could potentially enhance the efficacy of sip-T in mCRPC patients.
Clinical • PD(L)-1 Biomarker • IO biomarker
|
CD19 (CD19 Molecule) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CD69 (CD69 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • CD14 (CD14 Molecule) • FAS (Fas cell surface death receptor) • IL15 (Interleukin 15) • ITGAX (Integrin Subunit Alpha X) • LAMP2 (Lysosomal Associated Membrane Protein 2)
|
Provenge (sipuleucel-T)
2years
Prostate cancer immunotherapy: a review of recent advancements with novel treatment methods and efficacy. (PubMed, Am J Clin Exp Urol)
Sipuleucel-T (Provenge) is the first FDA approved immunotherapeutic agent for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (mCRPC); demonstrating a benefit in overall survival...There is also a need to adjust strategies to overcome histologic barriers such as tissue hypoxia and dense stroma. The racial differences of immunological responses between men of diverse ethnicities also merit further investigation to improve the efficacy of immunotherapy and better patient selection in prostate cancer.
Review • Journal • Tumor Mutational Burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CDK12 (Cyclin dependent kinase 12)
|
PD-L1 expression • MSI-H/dMMR • PD-L1 underexpression • TMB-L • CDK12 mutation
|
Provenge (sipuleucel-T)
over2years
A mutated prostatic acid phosphatase (PAP) peptide-based vaccine induces PAP-specific CD8+ T cells with ex vivo cytotoxic capacities in HHDII/DR1 transgenic mice (ITOC 2022)
Sipuleucel-T is the only FDA approved autologous cellular immunotherapy for PCa targeting prostatic acid phosphatase (PAP), showing a 4.1 month survival benefit for metastatic castration-resistant prostate cancer patients...The vaccine induced secretory (IFNγ and TNFα) and cytotoxic CD8+ T cells and effector memory splenic T cells. Conclusions The periphery of patients with PCa exhibits immune responsiveness to the MutPAP42mer peptide and immunization of mice induces/expands T cell-driven, wild-type PAP immunity, and therefore, has the potential to drive protective anti-tumour immunity in patients with PCa.
Preclinical • IO biomarker
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • CD4 (CD4 Molecule) • PSAP (Prostatic Acid Phosphatase)
|
Provenge (sipuleucel-T)
over2years
The Immunotherapy and Immunosuppressive Signaling in Therapy-Resistant Prostate Cancer. (PubMed, Biomedicines)
Only Sipuleucel-T and the immune checkpoint inhibitor pembrolizumab are approved by the US FDA for the treatment of limited prostate cancer patients. The purpose of this review is to summarize emerging advances in prostate cancer immunotherapy, with a particular focus on the molecular mechanisms that lead to immune evasion in prostate cancer. At the same time, we also highlight some potential therapeutic targets to provide a theoretical basis for the treatment of prostate cancer.
Review • Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
|
TMB (Tumor Mutational Burden)
|
Keytruda (pembrolizumab) • Provenge (sipuleucel-T)
over2years
Real-World Effectiveness of Sipuleucel-T on Overall Survival in Men with Advanced Prostate Cancer Treated with Androgen Receptor-Targeting Agents. (PubMed, Adv Ther)
This real-world study of mCRPC treatment indicates that men receiving sipuleucel-T and ARTAs had a longer median OS than patients receiving treatment with an ARTA alone, suggesting that leveraging mechanisms of action can be beneficial in treating patients with mCRPC.
Retrospective data • Journal • Real-world evidence
|
AR (Androgen receptor)
|
Xtandi (enzalutamide capsule) • abiraterone acetate • Provenge (sipuleucel-T)
over2years
Development of Cancer Immunotherapies. (PubMed, Cancer Treat Res)
Approval of the first therapeutic cancer vaccine, Sipuleucel-T, for the treatment of metastatic castration-resistant prostate cancer and the groundbreaking success and approval of immune checkpoint inhibitors and chimeric antigen receptor T cell therapy in the last decade, have driven an explosion of interest in and pursuit of novel cancer immunotherapy strategies. A broad range of modalities ranging from antibodies to adoptive T cell therapies is under investigation for the generalized treatment of a broad spectrum of cancers as well as personalized medicine. This chapter will focus on the recent advances, current strategies, and future outlook of immunotherapy development for the treatment of cancer.
Journal
|
IL2 (Interleukin 2)
|
Provenge (sipuleucel-T)
over2years
A Mutated Prostatic Acid Phosphatase (PAP) Peptide-Based Vaccine Induces PAP-Specific CD8 T Cells with Ex Vivo Cytotoxic Capacities in HHDII/DR1 Transgenic Mice. (PubMed, Cancers (Basel))
The periphery of patients with PCa exhibits immune responsiveness to the MutPAP42mer peptide and immunization of mice induces/expands T cell-driven, wild-type PAP immunity, and therefore, has the potential to drive protective anti-tumor immunity in patients with PCa.
Preclinical • Journal
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • PSAP (Prostatic Acid Phosphatase)
|
Provenge (sipuleucel-T)
over2years
High dimensional analysis of sipuleucel T from metastatic castration resistant prostate cancer patients using mass cytometry (AACR 2022)
This is the first comprehensive study to evaluate the composition of sip T from mCRPC patients using high dimensional CyTOF analysis. Given the increasing use of CyTOF in translational research, this data set serves as an important reference source, which could be used in future studies to help guide therapeutic modulation of activation/exhaustion markers to improve sip T efficacy and enhance beneficial immune responses.
Clinical • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • CD19 (CD19 Molecule) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • NCAM1 (Neural cell adhesion molecule 1) • ICOS (Inducible T Cell Costimulator) • CCR7 (Chemokine (C-C motif) receptor 7) • CD14 (CD14 Molecule) • CD86 (CD86 Molecule)
|
Provenge (sipuleucel-T)
3years
Dendritic Cells Pulsed with Cytokine-Adjuvanted Tumor Membrane Vesicles Inhibit Tumor Growth in HER2-Positive and Triple Negative Breast Cancer Models. (PubMed, Int J Mol Sci)
The only FDA approved DC-based immunotherapy to date is Sipuleucel-T, which utilizes a fusion protein to stimulate DCs ex vivo with GM-CSF and simultaneously deliver the antigen PAP for prostate cancer...Adaptive transfer of TMV-pulsed DCs to tumor bearing mice results in the inhibition of tumor growth, reduction in lung metastasis, and an increase in immune cell infiltration into the tumors. These observations suggest that DCs pulsed with TMVs containing GPI-GM-CSF and GPI-IL-12 can be further developed to be used as a personalized immunotherapy platform for cancer treatment.
Clinical • Preclinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 positive
|
Provenge (sipuleucel-T)
3years
IL-7 expands lymphocyte populations and enhances immune responses to sipuleucel-T in patients with metastatic castration-resistant prostate cancer (mCRPC). (PubMed, J Immunother Cancer)
Treatment with rhIL-7 led to a significant expansion of CD4+ and CD8+ T cells, and CD56 natural killer (NK) cells compared with observation after treatment with sip-T. The rhIL-7 treatment also led to improved antigen-specific humoral and T cell proliferative responses over time as well as to increased expression of activation markers and beneficial cytokines. This is the first study to evaluate the use of rhIL-7 after sip-T in patients with mCRPC and demonstrates encouraging results for combination approaches to augment beneficial immune responses.
Clinical • Journal • IO biomarker
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CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD4 (CD4 Molecule) • IL2 (Interleukin 2) • NCAM1 (Neural cell adhesion molecule 1) • TNFRSF9 (TNF Receptor Superfamily Member 9)
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IFNG expression • IL2 expression
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Provenge (sipuleucel-T) • CYT107