anti-PD-1 antibody / Tikcro Technologies, Weizmann Institute of Science - LARVOL DELTA

Squamous cell carcinoma arising in chronically damaged skin (Marjolin's Ulcer): still an unmet need in the era of immunotherapy. (PubMed, Oncologist) - "This study suggests that immunotherapy is less beneficial in SCC-MU. More work is needed to verify our findings and explore other treatment options."

IO biomarker • Journal • Tumor mutational burden • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • TMB

Crosslinking of Ly6a metabolically reprograms CD8 T cells for cancer immunotherapy. (PubMed, Nat Commun) - "Treatment with an anti-Ly6a antibody inhibits tumor growth in mice resistant to anti-PD1 therapy. Applying our findings in humans could lead to an immunotherapy treatment for patients with resistance to existing treatments."

Journal • Cutaneous Melanoma • Immunology • Melanoma • Oncology • Solid Tumor • MYC

Comparative study of immune response to local tumor destruction modalities in a murine breast cancer model. (PubMed, Front Oncol) - "The effects of combining RT, VTP, Cryo with anti-PD1 was also assessed...VTP and Cryo were associated with an increase in CD4+ and CD8+ cells in the periphery. These data suggest that cell death induced by VTP and Cryo elicit similar immune responses that differ from local RT."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • CD4 • CD8 • ITGAM

P-selectin as an emerging target for the treatment of primary and secondary brain tumors (AACR 2024) - P2 | "Thus, we have begun an investigator-initiated clinical trial, testing the efficacy of the anti-SELP antibody, Crizanlizumab, alone or in combination with anti-PD-1 antibody, Nivolumab, for GB and melanoma brain metastasis patients (NCT05909618). As such, it has the potential to reduce tumor burden and improve patient outcomes. This work can improve our understanding of GAMs function, which may pave the way for new and effective treatments for primary and secondary brain tumors."

IO biomarker • Brain Cancer • Breast Cancer • CNS Tumor • Glioblastoma • Glioma • Lung Cancer • Melanoma • Oncology • Solid Tumor • SELL • SELP

Spectrum of Response to Platinum and PARP Inhibitors in Germline BRCA-Associated Pancreatic Cancer in the Clinical and Preclinical Setting. (PubMed, Cancer Discov) - "Anti-PD-1 attenuated tumor growth in a novel humanized glBRCA PDAC PDX model...Additional treatment options for this unique subpopulation are needed. We generated model systems in PDXs and an ex vivo system (EVOC) that faithfully recapitulate these specific clinical scenarios as a platform to investigate the mechanisms of resistance for further drug development."

IO biomarker • Journal • Preclinical • Tumor mutational burden • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • BRCA • TMB

Characterization of molecular and spatial diversity of macrophages in hepatocellular carcinoma (SITC 2021) - P2 | "Our analysis of resected tumor from anti-PD-1 treated patients, will allow us to correlate MF programs, and direct T cell interaction, with clinical response, and will inform therapeutic trials targeting specific MF populations so as to improve clinical efficacy of cancer immunotherapy. Trial Registration NCT03916627"

IO biomarker • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CXCL9 • IL32 • S100A8

The use of medical cannabis concomitantly with immune checkpoint inhibitors in non-small cell lung cancer: A sigh of relief? (PubMed, Eur J Cancer) - "Preclinical and clinical data suggest no deleterious effect of cannabis on the activity of pembrolizumab as first-line monotherapy for advanced NSCLC. The differences in OS can most likely be attributed to higher disease burden and more symptomatic disease in the cannabis-treated group. These data provide reassurance regarding the absence of a deleterious effect of cannabis in this clinical setting."

Checkpoint inhibition • IO biomarker • Journal • Anorexia • Immune Modulation • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Palliative care • Solid Tumor • PD-L1

An activation to memory differentiation trajectory of tumor-infiltrating lymphocytes informs metastatic melanoma outcomes. (PubMed, Cancer Cell) - "Trajectory analysis of single-cell melanoma CD8 TILs also identified a high fraction of memory/resident memory-scoring TILs in anti-PD-1 responders, which expanded post therapy...Late/persistent, but not early activation signatures, prognosticate melanoma survival, and co-express with dendritic cell and IFN-γ response programs. These data identify an activation-like state associated to poor response and suggest successful memory conversion, above resuscitation of exhaustion, is an under-appreciated aspect of successful anti-tumoral immunity."

Journal • Immune Modulation • Inflammation • Melanoma • Oncology • Solid Tumor • CD8 • IFNG

Targeting purine synthesis in ASS1-expressing tumors enhances the response to immune checkpoint inhibitors. (PubMed, Nat Cancer) - "We further find that inhibiting purine synthesis increases pyrimidine to purine ratio, elevates expression of the immunoproteasome and significantly enhances the response of autologous primary CD8 T cells to anti-PD-1. These results suggest that treating patients with high-ASS1 cancers with purine synthesis inhibition is beneficial and may also sensitize them to immune checkpoint inhibition therapy."

Checkpoint inhibition • IO biomarker • Journal • Breast Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • ASS1 • CD8 • MYC

The interaction of CD4 helper T cells with dendritic cells shapes the tumor microenvironment and immune checkpoint blockade response. (PubMed, Nat Cancer) - "Reconstitution of Tht cells in vitro and in an ovalbumin-specific αβ TCR CD4 T-cell mouse model, shows that the Tht program is primed in tumor-draining lymph nodes by dendritic cells presenting tumor antigens, and that their function is important for harnessing the antitumor response of anti-PD-1 treatment. Our molecular and functional findings support the modulation of Tht-dendritic cell interaction checkpoints as a major interventional strategy in immunotherapy."

Biomarker • Checkpoint inhibition • Journal • Tumor microenvironment • Immune Modulation • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4

[VIRTUAL] Characterization of molecular and spatial diversity of macrophages in hepatocellular carcinoma (AACR 2021) - P2 | "Taken together, our data provide a new understanding of intratumoral MΦ diversity and highlight the presence of specific immunoregulatory MΦ programs unique to tumor lesions, with subsets of these MΦ found to be directly interacting with T cells, potentially modulating anti-tumor responsiveness. Our analysis of resected tumor from anti-PD-1 treated patients, will allow us to correlate MΦ programs, and direct T cell interaction, with clinical response, and will inform therapeutic trials targeting specific MΦ populations so as to improve clinical efficacy of cancer immunotherapy."

IO biomarker • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CXCL9 • IL32 • S100A8

Targeting Pin1 renders pancreatic cancer eradicable by synergizing with immunochemotherapy. (PubMed, Cell) - "Targeting Pin1 using clinically available drugs induces complete elimination or sustained remissions of aggressive PDAC by synergizing with anti-PD-1 and gemcitabine in diverse model systems. Mechanistically, Pin1 drives the desmoplastic and immunosuppressive TME by acting on CAFs and induces lysosomal degradation of the PD-1 ligand PD-L1 and the gemcitabine transporter ENT1 in cancer cells, besides activating multiple cancer pathways. Thus, Pin1 inhibition simultaneously blocks multiple cancer pathways, disrupts the desmoplastic and immunosuppressive TME, and upregulates PD-L1 and ENT1, rendering PDAC eradicable by immunochemotherapy."

Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CAFs • SLC29A1

[VIRTUAL] The recently approved high-TMB criteria may introduce a sex bias in response to PD1 inhibitors (AACR 2021) - "Motivation and research question: The U.S. Food and Drug Administration recently approved treatment with pembrolizumab, an immune checkpoint inhibitor (ICI) targeting PD1 (anti-PD1), for all advanced solid tumors with high tumor mutational burden (TMB), defined as ≥10 mutations/Megabase (mut/Mb). The FDA-approved criteria of 10 mutations/Mb could serve as an informative biomarker for stratifying female melanoma patients but is inadequate for stratifying male patients for anti-PD1 treatment. Our results indicate that its usage is likely to introduce a sex bias in additional cancer types, which will be highly important to carefully test further in larger datasets."

IO biomarker • Brain Cancer • Glioblastoma • Melanoma • Oncology • Solid Tumor • TMB