Immunotherapy coverage on Peptide News Digest is the peptide-side cross-section: cancer peptide vaccines, peptide-drug conjugates that combine targeting peptides with cytotoxic payloads, T-cell engagers built around peptide scaffolds, and HLA-restricted peptide presentation work.
Key threads: ELI-002 amphiphile-peptide vaccine (AMPLIFY-201), autogene cevumeran (BioNTech/Genentech), bicyclic peptide-payload conjugates from Bicycle Therapeutics, Verismo's KIR-CAR program, BriaCell's Bria-IMT in metastatic breast cancer, and Longhorn Vaccines' DRG5-BD11 peptidoglycan-based platform. Several AACR 2026 abstracts on peptide-MHC class II programs from Leukogene also land here.
Stories here cover trial readouts and platform launches. See #peptide-vaccine, #peptide-drug-conjugate, and #neoantigen for narrower threads.
Researchers at the First Affiliated Hospital of Henan University of Chinese Medicine reviewed 30 studies with 2,514 colorectal cancer patients, including 25 randomized trials, in which thymosin preparations were added to the same anticancer treatment, publishing in Frontiers in Oncology. After surgery, thymosin was linked to higher CD4 percentages, CD4/CD8 ratios, and natural killer cell percentages, and some trials reported better performance scores, but effects on neutropenia were inconclusive and only one trial gave comparable survival data. Certainty was low or very low, and the authors say current evidence does not support routine use.
Johns Hopkins University School of Medicine researchers reported in the Journal of Medicinal Chemistry on October 23, 2026 a structure-activity study of peptides derived from CKS1, identifying a proline hinge and the arrangement of water-loving and water-repelling amino acids as keys to how these peptides rupture cancer cell membranes. The lead, NF27, killed a broad range of cancer cells with little toxicity to healthy cells and low hemolysis, and the cell death it caused was immunogenic, drawing immune cells into mouse tumors. In mouse tumor models, NF27 suppressed growth and completely eradicated some tumors without observable systemic toxicity; no oncolytic peptide has been approved for clinical use.
University of California, San Francisco researchers reported in Clinical Cancer Research on October 21, 2026 a single-arm pilot of the PD-1 inhibitor pembrolizumab given with 177Lu-DOTATATE (Lutathera), a radioactive somatostatin-analog peptide, in 26 adults with grade 2 or 3 well-differentiated metastatic neuroendocrine tumors and a Ki-67 index above 10%, 20 of them grade 3. The objective response rate was 35%, median progression-free survival 13.3 months, and median overall survival 24.1 months, while severe adverse events occurred in 14 patients (54%). The authors concluded that the added benefit of the immunotherapy remains unclear and that the severe side-effect rate was higher than expected for Lutathera alone.
A Nature Communications paper from a Texas A&M Health team published May 19 reported the engineering of genetically encoded calcium release-activated calcium channel (CRAC) inhibitory binders called CRABs — peptide inhibitors derived from the ORAI C-terminal tail that selectively interfere with STIM1-ORAI coupling. The plasma-membrane-anchored CRAB variant potently inhibits calcium influx and downstream NFAT signaling. The platform spans optogenetic (Opto-CRAB) and chemogenetic (Chemo-CRAB) variants for graded, real-time control of CRAC activity. In a zebrafish Stormorken syndrome model, CRABs rescued thrombocyte progenitor production. The therapeutic implication: a peptide-based adjustable brake on T-cell calcium signaling that could enable safer, more controllable immune cell therapies — CAR-T cytokine release moderation, autoimmune T-cell quenching, transplantation tolerance induction.
Recent reviews and real-world observation studies aggregate the state of peptide-vaccine immunotherapy for glioblastoma. A 2024 Nature Communications real-world observational study reported clinically meaningful outcomes for personalized peptide vaccines; the UCPVax + temozolomide trial (NCT04280848) showed 97% anti-TERT immune response, 48% epitope spread, median OS 17.9 months, and 26% alive at 2 years. The peptide-vaccine modality is one of multiple approaches (mRNA, dendritic cell, neoantigen) advancing alongside immune checkpoint blockade.
BriaCell's Bria-IMT + checkpoint inhibitor combination preserved overall health status and key functional quality-of-life measures in its pivotal Phase 3 study in heavily pretreated metastatic breast cancer patients who had failed ADC, CPI, and CDK4/6 inhibitor therapy. Phase 2 biomarker analyses identified mitotic circulating tumor cells as prognostic and PD-L1 in tumor-macrophage fusion cells as predictive of checkpoint benefit. Presented at AACR April 20.
Nearly half of participants in a Phase 1 trial of BioNTech/Genentech's personalized mRNA neoantigen vaccine autogene cevumeran remain alive up to six years after treatment, with T-cell responses showing no signs of waning. Eight of 16 patients produced durable CD8+ T cells targeting tumor neoantigens after nine doses, with the immune memory still detectable at six-year follow-up. A Phase 2 trial is underway.
A comprehensive review in Discover Oncology highlights antimicrobial peptides' emerging dual role as anticancer and antiviral therapeutics. AMPs selectively target cancer cell membranes through electrostatic interactions while also demonstrating antiviral activity, with their immunomodulatory properties and reduced resistance development offering advantages over conventional chemotherapy.
A Phase 1 trial published in Nature Medicine showed that FLC-Vac, a therapeutic peptide vaccine targeting the DNAJ-PKAc fusion protein in fibrolamellar hepatocellular carcinoma, combined with nivolumab and ipilimumab achieved 75% disease control (9/12 patients) and 25% partial response rate. All responders showed tumor-specific T cell responses.
A randomized Phase I/II trial of a melanoma helper peptide vaccine with anti-CD27 antibody varlilumab reported 69% four-year disease-free survival in the combination arm versus 20% with vaccine alone. However, varlilumab depleted circulating CD4+ T cells, potentially limiting vaccine synergy and warranting further optimization.