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DRUG CLASS:

CD70-targeted CAR-T immunotherapy

11d
A Clinical Study of CHT101 in CD70-Positive Advanced Solid Tumors (clinicaltrials.gov)
P1, N=36, Recruiting, Tianjin Medical University Cancer Institute and Hospital
New P1 trial • Metastases
21d
Safety and activity of CTX130, a CD70-targeted allogeneic CRISPR-Cas9-engineered CAR T-cell therapy, in patients with relapsed or refractory T-cell malignancies (COBALT-LYM): a single-arm, open-label, phase 1, dose-escalation study. (PubMed, Lancet Oncol)
In patients with heavily pretreated T-cell lymphoma, CTX130 showed manageable safety and a promising objective response rate. This study shows that allogeneic, readily available CAR T cells can be safely given to patients with relapsed or refractory T-cell lymphoma. A next-generation CAR T-cell therapy containing additional potency gene edits (CTX131) is in clinical development.
P1 data • Journal • CAR T-Cell Therapy
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CD70 (CD70 Molecule)
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cyclophosphamide • fludarabine IV • CTX130 • CTX131
1m
CD70 CAR T cells secreting an anti-CD33/anti-CD3 dual targeting antibody overcome antigen heterogeneity in AML. (PubMed, Blood)
Additionally, CD33 TEAMs successfully redirected T cells isolated from AML patients to activate, secrete cytokines, and kill tumor targets despite exposure to substantial prior cytotoxic therapies. In summary, our findings demonstrate the feasibility of our 7033 CAR to overcome AML heterogeneity and leverage the bystander T cells of patients; this approach warrants further study in patients with this dire clinical need.
Journal • CAR T-Cell Therapy • IO biomarker
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CD33 (CD33 Molecule) • CD70 (CD70 Molecule)
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CD70-directed CAR-T
2ms
Enrollment open • CAR T-Cell Therapy • Metastases
3ms
CAR T-cell Therapy Directed to CD70 for Pediatric Patients With Hematological Malignancies (clinicaltrials.gov)
P1, N=24, Recruiting, St. Jude Children's Research Hospital | Initiation date: Sep 2024 --> Dec 2024
Trial initiation date • CAR T-Cell Therapy
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CD70 (CD70 Molecule)
|
cyclophosphamide • fludarabine IV • mesna
3ms
New P1 trial • CAR T-Cell Therapy • Metastases
4ms
Study of Therapeutic Efficacy of CAR-T Cell Therapy in Patients With MDR-SRNS (clinicaltrials.gov)
P1, N=18, Recruiting, The Children's Hospital of Zhejiang University School of Medicine
New P1 trial • CAR T-Cell Therapy
5ms
Enrollment open
|
CTX131
6ms
New P1/2 trial
|
CTX131
6ms
Knocking out CD70 rescues CD70-specific nanoCAR T cells from antigen-induced exhaustion. (PubMed, Cancer Immunol Res)
On the other hand, the gene signature of KO CD70-specific nanoCAR T cells overlapped with the gene signature of CAR T-cell infusion products that led to complete responses in chronic lymphatic leukemia patients. Our data show that CARs targeting endogenous T-cell antigens negatively affect CAR T-cell functionality by inducing an exhausted state, which can be overcome by knocking out the specific target.
Journal • CAR T-Cell Therapy
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CD70 (CD70 Molecule)
6ms
CAR T-cell Therapy Directed to CD70 for Pediatric Patients With Hematological Malignancies (clinicaltrials.gov)
P1, N=24, Recruiting, St. Jude Children's Research Hospital | Not yet recruiting --> Recruiting
Enrollment open • CAR T-Cell Therapy
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CD70 (CD70 Molecule)
|
cyclophosphamide • fludarabine IV • mesna
8ms
New P1 trial
|
CD70 (CD70 Molecule)
|
cyclophosphamide
9ms
CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma. (PubMed, Cancer Discov)
Finally, we report on a next-generation CAR T construct, CTX131, in which synergistic potency edits to CTX130 confer improved expansion and efficacy in preclinical studies. Although the role of CAR T cells is well established in hematologic malignancies, the clinical experience in solid tumors has been disappointing. This clinical trial demonstrates the first complete response in a patient with RCC, reinforcing the potential benefit of CAR T cells in the treatment of solid tumors.
Journal • CAR T-Cell Therapy • Metastases
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CD70 (CD70 Molecule)
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CTX130 • CTX131
9ms
A Safety and Efficacy Study Evaluating CTX130 in Subjects With Relapsed or Refractory T or B Cell Malignancies (COBALT-LYM) (clinicaltrials.gov)
P1, N=45, Active, not recruiting, CRISPR Therapeutics AG | Recruiting --> Active, not recruiting
Enrollment closed
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CTX130
11ms
New P1 trial • Metastases
|
CD70 (CD70 Molecule)
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cyclophosphamide • CD70 CAR-T
1year
CD70 CXCR2-Modified CAR T-Cells Against Acute Myeloid Leukemia (TCT-ASTCT-CIBMTR 2024)
8R-70CAR T cells are able to specifically recognize and kill CD70+ AML cells, and cytotoxicity may be augmented by enhancing CD70 expression with azacytidine pre-treatment. A LLS tumoroid model can aid in 3D visualization of 8R-70CAR T cells interactions AML cells. These findings combined with safety data obtained from our ongoing phase I clinical trial for adults with glioblastoma (NCT05353530) will support expansion of our existing IND to treat patients with AML using our novel 8R-70CAR.
CAR T-Cell Therapy
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IFNG (Interferon, gamma) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • CD70 (CD70 Molecule) • CXCR2 (Chemokine (C-X-C motif) receptor 2)
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MLL rearrangement • CD70 expression • IFNG expression • CXCL8 expression • CXCL8 overexpression
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azacitidine • 8R-70CAR T
1year
Evaluation of CD70 Chimeric Antigen Receptor T (CAR-T) Cells As a Potential Treatment for Non-Hodgkin's Lymphoma: A Preclinical Study (ASH 2023)
We successfully generated CD70 CAR-T cells based on a VHH nanobody (11C9) and CD19 CAR-T cells based on murine scFv (FMC63) following the exact manufacturing protocols used for phase I and phase II clinical trial products respectively... Our results indicate that CD70 CAR-T cell is potential treatment for NHL. We will conduct an investigation of single and dual CD70 CAR-T on treatment of lymphoma especially for CD19 negative NHL.
Preclinical • CAR T-Cell Therapy • IO biomarker
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TNFA (Tumor Necrosis Factor-Alpha) • CD70 (CD70 Molecule)
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CD70 expression
1year
Efficacy and Safety of Chimeric Antigen Receptor T Cells Therapy Strategy with Dual Targeting of CD19 and CD70 to Treat Relapsed/Refractory Diffuse Large B-Cell Lymphoma (ASH 2023)
All patients received cyclophosphamide/fludarabine chemotherapy conditioning 1-2 days before infusions of CAR-T cells. In summary, our research data confirms that the efficacy and safety of CD19/CD70 dual targeted CAR-T cells infusion, continued follow-up will determine whether the CD19/CD70 CAR-T cells therapy can obtain long term overall survival in our study. How to further improve the efficacy and safety of dual target CAR-T is still worth exploring. It's needed to optimize multi-specific targeting by CAR-T cells to improve the efficacy both in B cell malignancies and other hematological malignancies.
Clinical • CAR T-Cell Therapy • IO biomarker
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CD70 (CD70 Molecule) • CD27 (CD27 Molecule) • CASP9 (Caspase 9)
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CD19 expression
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cyclophosphamide • fludarabine IV
1year
TRAVERSE: Safety and Efficacy of ALLO-316 in Subjects With Advanced or Metastatic Clear Cell Renal Cell Carcinoma (clinicaltrials.gov)
P1, N=120, Recruiting, Allogene Therapeutics | Trial primary completion date: Dec 2022 --> Aug 2025
Trial primary completion date • Metastases
|
cyclophosphamide • fludarabine IV • ALLO-316 • ALLO-647
over1year
New P1 trial • Metastases
|
IL6 (Interleukin 6) • CD70 (CD70 Molecule)
|
CD70 expression
|
cyclophosphamide • CD70 CAR-T
over1year
New P1 trial • CAR T-Cell Therapy • Metastases
|
IL6 (Interleukin 6) • CD70 (CD70 Molecule) • IL2 (Interleukin 2)
over1year
Phase I Study of IL-8 Receptor-modified CD70 CAR T Cell Therapy in CD70+ and MGMT-unmethylated Adult Glioblastoma (IMPACT) (clinicaltrials.gov)
P1, N=18, Recruiting, University of Florida | Not yet recruiting --> Recruiting | Trial completion date: Dec 2041 --> Dec 2042 | Trial primary completion date: Dec 2026 --> Dec 2027
Enrollment open • Trial completion date • Trial primary completion date • CAR T-Cell Therapy
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MGMT (6-O-methylguanine-DNA methyltransferase) • CD70 (CD70 Molecule)
|
8R-70CAR T
over1year
New P1/2 trial • CAR T-Cell Therapy
|
IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CD70 (CD70 Molecule) • IL2 (Interleukin 2) • IL10 (Interleukin 10)
|
CD70 expression
|
cyclophosphamide • CD70 CAR-T
over1year
New P1/2 trial
|
IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CD70 (CD70 Molecule) • IL2 (Interleukin 2) • IL10 (Interleukin 10)
|
CD70 expression
|
albumin-bound paclitaxel • cyclophosphamide • CD70 CAR-T
over1year
Preclinical development and evaluation of nanobody-based CD70-specific CAR T cells for the treatment of acute myeloid leukemia. (PubMed, Cancer Immunol Immunother)
CD70 expression in AML blasts was not fully supportive of its role in AML targeted therapy as reported. The combinational use of Chidamide and Decitabine with nb70CAR-T could provide a new potential for the treatment of AML.
Preclinical • Journal • CAR T-Cell Therapy • IO biomarker
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CD70 (CD70 Molecule) • CD27 (CD27 Molecule)
|
CD70 expression
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decitabine • Epidaza (chidamide)
over1year
Phase I Study of IL-8 Receptor-modified CD70 CAR T Cell Therapy in CD70+ and MGMT-unmethylated Adult Glioblastoma (IMPACT) (clinicaltrials.gov)
P1, N=18, Not yet recruiting, University of Florida | Trial completion date: Dec 2040 --> Dec 2041 | Trial primary completion date: Dec 2025 --> Dec 2026
Trial completion date • Trial primary completion date • CAR T-Cell Therapy
|
MGMT (6-O-methylguanine-DNA methyltransferase) • CD70 (CD70 Molecule)
|
8R-70CAR T
over1year
A Safety and Efficacy Study Evaluating CTX130 in Subjects With Relapsed or Refractory Renal Cell Carcinoma (COBALT-RCC) (clinicaltrials.gov)
P1, N=107, Active, not recruiting, CRISPR Therapeutics AG | Recruiting --> Active, not recruiting
Enrollment closed • Metastases
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CTX130
almost2years
CD70-targeting CAR-T and CAR-NK cells demonstrate potent activity against NSCLC drug-tolerant persister cells (AACR 2023)
In a patient-derived xenograft model of HER2YVMA mutant lung cancer, we observed that HER2 CAR-NK cells showed enhanced antitumor activity in mice treated with the HER2 inhibitor, poziotinib, for two weeks, compared to CAR-NK cells only, poziotinib only, or mice treated upfront with HER2 CAR-NK cells plus poziotinib. Furthermore, we determined that CD70-targeting CAR-T and CAR-NK cells showed promising in vitro activity against the DTPCs of osimertinib-treated EGFR mutant NSCLC. These results demonstrate CAR-based cellular therapy as an effective approach to target DTPCs and identify CD70 as a novel therapeutic target for combatting DTPCs in NSCLC.
IO biomarker
|
KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • CD70 (CD70 Molecule)
|
EGFR mutation • HER-2 YVMA
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Tagrisso (osimertinib) • Pozenveo (poziotinib)
almost2years
Preclinical evaluation of CD70-specific CAR T cells targeting acute myeloid leukemia. (PubMed, Front Immunol)
Our study reveals that anti-CD70 CAR-T cells are a new potential treatment for AML. However, such CAR-T cell therapy did not completely eliminate leukemia in vivo, suggesting that future studies aiming to generate innovative combinatorial CAR constructs or to increase CD70 expression density on leukemia cell surface to prolong the life-span of CAR-T cells in the circulation will be needed in order to optimize CAR-T cell responses for AML.
Preclinical • Journal • CAR T-Cell Therapy • IO biomarker
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CD70 (CD70 Molecule)
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CD70 expression
almost2years
CD70 is a therapeutic target upregulated in EMT-associated EGFR tyrosine kinase inhibitor resistance. (PubMed, Cancer Cell)
Anti-CD70 antibody drug conjugates (ADCs) and CD70-targeting chimeric antigen receptor (CAR) T cell and CAR NK cells show potent activity against EGFR TKI-resistant cells and DTPCs. These results identify CD70 as a therapeutic target for EGFR mutant tumors with acquired EGFR TKI resistance that merits clinical investigation.
Journal
|
EGFR (Epidermal growth factor receptor) • CD70 (CD70 Molecule)
|
EGFR mutation
2years
Developing CD70-Targeted CAR-T Cells for the Treatment of Hematological and Solid Malignancies (ASH 2022)
Furthermore, the CD70 CAR T cells displayed potent anti-tumor activities, as evident by in vitro killing against CD70 expressed cell lines, such as Molm-13, an AML cell line, or ACHN, a RCC cell line; and by in vivo tumor inhibition and clearance in immunodeficient xenograft mouse model. Together, our data support the further development of CD70-targeted CAR-T cells for the treatment of hematological and solid malignancies.
CAR T-Cell Therapy • IO biomarker
|
CD8 (cluster of differentiation 8) • CD70 (CD70 Molecule)
|
CD70 expression
2years
Going after CD70 with CAR T, NK Cells. (PubMed, Cancer Discov)
CD70 has emerged as a promising solid tumor target for chimeric antigen receptor (CAR)-bearing T or natural killer (NK) cells, with one allogeneic CAR T-cell therapy, CTX130, showing preliminary efficacy in renal cell carcinoma. Further, assessments of a cord blood-derived CAR-NK alternative have started; the trial will be the first to use cryopreserved NK cells.
Journal
|
CD70 (CD70 Molecule)
|
CTX130
2years
Novel cellular therapies to achieve cures in clear cell renal cell carcinoma (KCRS 2022)
Impact and Innovation: Building on our long-term research of developing ccRCC cellular therapy, we anticipate filing an Investigational New Drug application and advancing second-generation DFIR-CAR T to clinic after completion of these studies. Significant scientific advances will be made to overcome the barriers that have prevented this promising "living drug" therapy to be developed for patients with advanced ccRCC and to deliver safe and effective therapy.
PD(L)-1 Biomarker • IO biomarker
|
CD70 (CD70 Molecule) • CA9 (Carbonic anhydrase 9)
|
CA9 expression
over2years
New P1 trial
|
IL6 (Interleukin 6) • CD70 (CD70 Molecule)
|
CD70 expression
|
cyclophosphamide • CD70 CAR-T
over2years
Trial initiation date • CAR T-Cell Therapy
|
MGMT (6-O-methylguanine-DNA methyltransferase) • CD70 (CD70 Molecule)
|
8R-70CAR T
over2years
New P1 trial
|
IL6 (Interleukin 6) • CD70 (CD70 Molecule)
|
CD70 expression
|
cyclophosphamide • CD70 CAR-T
over2years
New P1 trial
|
IL6 (Interleukin 6) • CD70 (CD70 Molecule)
|
CD70 expression
|
cyclophosphamide • CD70 CAR-T
over2years
New P1 trial
|
IL6 (Interleukin 6) • CD70 (CD70 Molecule)
|
CD70 expression
|
cyclophosphamide • CD70 CAR-T
over2years
CD70 CAR T cells in AML: Form follows function. (PubMed, Cell Rep Med)
Using a multimodal approach toward developing a new CD70-targeted Chimeric antigen receptor (CAR) T cell in acute myeloid leukemia, Leick et al. report on their synergetic strategy, which incorporates both CAR T cell construct modifications with enhancement of leukemia antigen expression to improve CAR T cell functionality.
Journal • CAR T-Cell Therapy
|
CD70 (CD70 Molecule)