HLA-A*02

Our study also suggested genetic heterogeneity between Asian and European populations by identifying ancestry-specific genetic associations. Overall, this study has implicated novel disease genes and molecular mechanism for DLBCL.

The combination of DAC/αPD-L1 shows promise in improving HBV-specific T cell responses in vitro, highlighting the potential of remodeling exhaustion-associated epigenetic signatures to enhance HBV-specific T cell restoration and suggesting a novel immunotherapeutic avenue for CHB.

P2, N=66, Active, not recruiting, Adaptimmune | Recruiting --> Active, not recruiting

Our findings indicate that NY-ESO-1 TCR-transduced T cells have the potential to mediate dual antitumor effects through both antigen-independent NK-like and antigen-specific CTL-like responses. This study underscores the potential of NY-ESO-1 TCR-T cells as potent tumor-eradicating agents, highlighting the importance of harnessing their versatile functional capabilities to refine and enhance therapeutic strategies.

P1, N=20, Completed, University Hospital Tuebingen | Active, not recruiting --> Completed

P3, N=680, Recruiting, Immunocore Ltd | Trial primary completion date: Dec 2026 --> Oct 2027

P3, N=540, Recruiting, Immunocore Ltd | Trial completion date: Sep 2027 --> Jul 2028 | Trial primary completion date: Dec 2026 --> Mar 2028 | Phase classification: P2/3 --> P3

Extensive HLA-A*02 and antigen expression testing was performed to identify potential participants. Lete-cel was generally well tolerated and had no unexpected AEs. Anti-tumor activity was observed in a limited number of patients.

These findings suggest that leveraging the TCR machinery is a promising strategy for enhancing pMHC-targeted CAR-T cell therapy for solid tumors, potentially leading to more effective treatments.

Notably, approximately 64% of liver tumors expressed one or more TAAs associated with these 21 peptides, positioning them as promising candidates for liver cancer therapies, such as peptide vaccines or T cell receptor (TCR)-T cell treatments. This study highlights the power of integrating computational and experimental approaches to discover TAAs for immunotherapy.

Opt TCR-T cells exhibited higher TCR transduction efficiency, higher TCR expression levels, higher avidity, and greater cytotoxicity than did Ori TCR-T cells. These results suggest that HLA-A*02:01/CLSPN1254-1262 specific Opt TCR-T cells are promising candidates for CDDP combination therapy.

Furthermore, the frequency of effector WT1126-CTLs positively correlated with WT1126-CTL clonality in PTs; whereas, the frequency of naïve phenotype WT1126-CTLs tended to be negatively correlated with clonality. In conclusion, these results suggest that the WT1 protein in tumor cells is highly immunogenic, thereby stimulating endogenous naïve-type WT1126-CTLs and enabling them to clonally expand and differentiate into effector-type WT1126-CTLs.

P=N/A, N=1200, Recruiting, PharmaEssentia

P1/2, N=7, Terminated, Fred Hutchinson Cancer Center | Trial completion date: Jan 2025 --> Jan 2024 | Active, not recruiting --> Terminated; Terminated due to insufficient funding

P1/2, N=727, Recruiting, Immunocore Ltd | Trial primary completion date: Jun 2026 --> Feb 2026

P1, N=9, Active, not recruiting, Fred Hutchinson Cancer Center | Recruiting --> Active, not recruiting | N=15 --> 9

P2, N=7, Active, not recruiting, Adaptimmune | Trial completion date: Jul 2024 --> Jul 2025

P1/2, N=0, Withdrawn, Immunocore Ltd | N=75 --> 0 | Terminated --> Withdrawn

P1, N=0, Withdrawn, Immunocore Ltd | N=180 --> 0 | Recruiting --> Withdrawn

In August 2024, afamitresgene autoleucel was approved in the USA under accelerated approval for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P or -A*02:06P positive and whose tumour expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices. This article summarizes the milestones in the development of afamitresgene autoleucel leading to this first approval for the treatment of advanced synovial sarcoma.

P1, N=22, Active, not recruiting, University Health Network, Toronto | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

Potent activation of WT1-specific immune responses through a combination chemoimmunotherapy regimen including the WT1-DC vaccine in patients with UR-PDAC may modulate the TME and enable conversion surgery, resulting in clinical benefits (Online supplemental file 1).

a May occur at any point in disease course. CRC, colorectal cancer; D, day; MESO, mesothelioma; NSCLC, non-small cell lung cancer; OVCA, ovarian cancer; PANC, pancreatic cancer; PCLD, preconditioning lymphodepletionDownload figure Open in new tab Download powerpoint Abstract 627 Figure 3 EVEREST-2 phase 1 dose escalation study design

β2M shRNA, beta–2–microglobulin short–hairpin RNA; CD, cluster of differentiation; EF1α, elongation factor–1 alpha; LIR, leukocyte immunoglobulin–like receptor; scFv, single–chain variable fragment; T2A, thosea asigna virus 2ADownload figure Open in new tab Download powerpoint Abstract 588 Figure 2 EVEREST-1 study design. BOIN, Bayesian optimal interval design; PCLD, preconditioning lymphodepletion; RP2D, recommended phase 2 dose

These findings serve as a proof-of-concept for using multiple immunogenic peptides as a novel therapeutic approach in TNBC patients.

P1/2, N=73, Active, not recruiting, PDC*line Pharma SAS | Trial primary completion date: Dec 2025 --> Jul 2024

This table includes patients enrolled in BASECAMP-1 with germline HLA-A*02 LOH status and correlative data available. Data as of 01 June 2024

Treatment options are limited to Tebentafusp in patients with HLA-A*02:01 mutation with immunotherapy and chemotherapy yielding poor results...In a recent phase I trial of a PRMT5 inhibitor, PRT811, clinical activity was described in cases of CAUM. 676 CAUM and 9666 CASM patients underwent hybrid capture based CGP to evaluate genomic alterations (GA)... Although MTAP loss is less frequent in CAUM than in CASM, the recent evidence that this genomic alteration predicts responsiveness to PRMT5 inhibition is noteworthy. This highlights the importance of further investigating this biomarker for patients with this rare and clinically aggressive type of cancer.

Our findings suggest that the components of the PLC editing module serve a dual role, acting not only as peptide proofreaders but also as limiters for abundant peptides. This dual function ensures the presentation of a broad spectrum of antigenic peptides.

SPLICE-neo is the first tool to comprehensively identify and prioritize splicing neoantigens from both DNA splice-site mutations and de novo RNA aberrant splicings. There are two major advances of SPLICE-neo. First, we developed novel logic models that assemble and prioritize full-length aberrant transcripts from DNA splice-site mutations. Second, SPLICE-neo can identify exon-skipping events involving more than two exons, which account for a quarter to one-third of all skipping events.

P1, N=44, Recruiting, M.D. Anderson Cancer Center | Suspended --> Recruiting

P1, N=12, Terminated, GlaxoSmithKline | Trial completion date: Dec 2025 --> Jun 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Jun 2023; The study was terminated due to a change in GSK's R&D priorities.

P1/2, N=40, Suspended, Fred Hutchinson Cancer Center | Recruiting --> Suspended

To conclude, we suspect that the discrepancies between NGS and RT-PCR results were caused by the presence of a significant amount of circulating lymphoma cells in the peripheral blood sample. Lymphomagenic mutations may involve the histocompatibility antigen coding region and affect HLA expressed on malignant cells. This finding may be relevant for the selection of test material in primary and confirmatory HLA testing in patients with active hematological malignancies because of the strong impact of incorrect HLA typing on the procedure of a donor selection.

P1, N=29, Completed, University of Pennsylvania | Active, not recruiting --> Completed | Trial completion date: Sep 2024 --> Feb 2024 | Trial primary completion date: Sep 2024 --> Feb 2024

In patients with incurable HPV16+ solid tumors treated with SQZ-PBMC-HPV, an increase in CD8+ T cell density within the tumor parenchyma was associated with superior disease control rate and overall survival. The product composition for patients with increased CD8+ T cell density was enriched for T cells.

We also found that the in vitro activity of IgG-T-TCE-NY could be leveraged by various anti-CD3 antibodies and Fc silencing. The IgG-T-TCE-NY efficiently inhibited tumor growth in a tumor-PBMC co-engrafted mouse model without any obvious toxicities.

However, a single-signaling domain chimeric antigen receptor (ssdCAR) targeting L1CAM, a cell adhesion protein frequently overexpressed in HPV16-induced cancer, prompted a synergistic effect that significantly enhanced the cytotoxic capacity of NK-92/CD3/CD8 cells armored with both TCR and ssdCAR when both receptors simultaneously engaged their respective targets, as shown by live microscopy of 2-D and 3-D co-cultures. Thus, virus-specific TCRs from the CD8+ T cell repertoire of healthy donors can be combined with a suitable ssdCAR to enhance the cytotoxic capacity of the effector cells and, indirectly, their specificity.

P2, N=103, Active, not recruiting, Adaptimmune | Trial primary completion date: Nov 2022 --> Aug 2024

P | "Clinical Trial Registration Number: NCT04981119"

P2, N=3, Terminated, Adaptimmune | N=45 --> 3 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2023 --> Apr 2023; Study was terminated due to difficulty recruiting subjects and lack of efficacy

P1/2, N=47, Terminated, Sumitomo Pharma America, Inc. | Phase classification: P1b/2 --> P1/2 | Completed --> Terminated; Sponsor's decision to terminate development of the program.