HLA-A (Major Histocompatibility Complex, Class I, A)

PRAME is highly and frequently expressed in NUT carcinoma, and the most common oncoprotein causing NUT carcinoma, BRD4::NUTM1, contributes to these high PRAME levels. PRAME epitopes presented by HLA class I are a previously unrecognized therapeutic vulnerability for NUT carcinoma that warrants clinical trials testing PRAME-targeted immunotherapies in this neglected patient population.

MTX-241F changes the glioma immunopeptidome, unveiling H2B1K, brain-enriched, and treatment-induced immunopeptides as immunologically visible targets. These findings provide a rationale for integrating molecularly targeted therapy with immunotherapeutic approaches to enhance tumor recognition and treatment efficacy in DMG and GBM.

These findings demonstrate the feasibility of targeting dysregulated tumor suppressor proteins with TCR-T cell therapeutics and identify p14ARF as a promising target for future therapies.

Plasma analysis identified a pathogenic SPEN variant and human leukocyte antigen (HLA) genotype (HLA-A*02:17 and HLA-A*02:01 alleles), conferring therapeutic eligibility for tebentafusp, and molecular evidence supportive of metastatic uveal melanoma, enabling initiation of appropriate systemic therapy before additional tissue sampling...While the liquid biopsy and ablation of one of the lesions confirmed the diagnosis, the liquid biopsy was a key first step that provided a comprehensive diagnostic and prognostic picture without the need for an invasive procedure. This case highlights how integrating liquid biopsy into the diagnostic pathway for uveal melanoma can lead to earlier, more informed treatment decisions.

Three early-phase OV studies, totaling twenty-nine patients, yielded no radiographic responses but showed tumor-specific T-cell expansion and transient disease stabilization. Safety profiles reflected the mechanism of action: tebentafusp most often caused rash, pyrexia, and usually manageable cytokine-release syndrome with grade-3+ events in 40-70% yet discontinuation in roughly 2%; TIL therapy toxicity was driven by lymphodepleting chemotherapy and high-dose interleukin-2 with one treatment-related death; and OVs were generally well tolerated with no more than 20% grade-3 events.

Meanwhile, the pan-A*02-TCR-T cells also showed enhanced cytokine production, superior tumor cell killing, and achieved complete tumor eradication in murine models. This study developed an AFP-specific TCR-T with fine-tune affinity, demonstrating remarkable preclinical efficacy and safety, alongside a sequence-optimized version with pan-HLA-A*02 applicability, offering broader patient access and therapeutic versatility.

The comparison of painful and nonpainful samples highlights several changes in cellular composition, transcriptome and inferred molecular signaling linked specifically with the presence of pain, and also a novel role for HLA-A in neuropathic pain. Our findings represent a valuable resource for pain research, highlighting the role of inflammation, endothelial cell dysfunction, and chemokine signaling in neuropathic pain.

In striking contrast to the bispecific antibody results, increasing CAR affinity decreased function in each CAR format due to lower T cell activation upon interaction with target cancer cells. These results have important implications for the design of future immunotherapeutic approaches targeting low-density antigens.

Subsequent treatment with paclitaxel plus cetuximab also led to disease progression after two months...Third-line therapy with 5-FU, carboplatin, and pembrolizumab achieved a partial response, but disease progression occurred after nine months...Additionally, acquired MYC amplification may contribute to resistance to chemotherapy and pembrolizumab. These findings underscore the importance of personalized treatment strategies in SCC patients with specific genomic alterations.

In contrast, given the extremely weak MHC affinity and resultant short-lived cell surface pMHC expression, the common p53 neoepitope R175H/HLA-A*02:01 escapes immune selection despite CTL with high quality T-cell receptors. Rigorous tumour-protective immunoediting makes effective truncal neoepitope targeting a challenge, requiring attentive MS analysis and functional vetting to focus protective cytolytic responses.

P1/2, N=474, Recruiting, A2 Biotherapeutics Inc. | N=230 --> 474

These findings validate the broader utility of the previously identified HER2/neu-specific TCR repertoire and elucidate the molecular mechanisms driving its therapeutic efficacy, demonstrating the potential of TCR-T cells for treating solid tumors through robust cytotoxic activity and the emergence of a favorable CD4+CD8+ T cell population. This study offers critical mechanistic insights, establishing a foundation for advancing TCR-engineered therapies toward clinical use in HER2/neu-positive cancers.