- |||||||||| Adakveo (crizanlizumab-tmca) / Novartis, Opdivo (nivolumab) / Ono Pharma, BMS
P-selectin as an emerging target for the treatment of primary and secondary brain tumors (Section 3) - Mar 5, 2024 - Abstract #AACR2024AACR_6905;
P2
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.
- |||||||||| anti-PD-1 antibody / Tikcro Technologies
Journal: Modeling T cell temporal response to cancer immunotherapy rationalizes development of combinatorial treatment protocols. (Pubmed Central) - Mar 2, 2024
We demonstrate that combining anti-PD-1 therapy with anti-4-1BB agonist enhances the recruitment and proliferation of activated precursors, resulting in tumor control. These data suggest that effective response to anti-PD-1 therapy is dependent on sufficient influx of activated precursor CD8+ cells to the TME and highlight the importance of understanding system-level dynamics in optimizing immunotherapies.
- |||||||||| anti-PD-1 antibody / Tikcro Technologies
Preclinical, Journal, Tumor mutational burden, BRCA Biomarker, PARP Biomarker, PD(L)-1 Biomarker, IO biomarker: Spectrum of Response to Platinum and PARP Inhibitors in Germline BRCA-Associated Pancreatic Cancer in the Clinical and Preclinical Setting. (Pubmed Central) - Aug 7, 2023
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.
- |||||||||| anti-PD-1 antibody / Tikcro Technologies
Journal, Tumor-Infiltrating Lymphocyte: An activation to memory differentiation trajectory of tumor-infiltrating lymphocytes informs metastatic melanoma outcomes. (Pubmed Central) - May 17, 2022
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.
- |||||||||| anti-PD-1 antibody / Tikcro Technologies
Biomarker, Journal, Checkpoint inhibition, Tumor microenvironment: The interaction of CD4 helper T cells with dendritic cells shapes the tumor microenvironment and immune checkpoint blockade response. (Pubmed Central) - Apr 20, 2022
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.
- |||||||||| anti-PD-1 antibody / Tikcro Technologies
Journal, Checkpoint inhibition, PD(L)-1 Biomarker, IO biomarker: Targeting purine synthesis in ASS1-expressing tumors enhances the response to immune checkpoint inhibitors. (Pubmed Central) - Apr 15, 2022
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.
- |||||||||| anti-PD-1 antibody / Tikcro Technologies
Journal: Targeting Pin1 renders pancreatic cancer eradicable by synergizing with immunochemotherapy. (Pubmed Central) - Jan 5, 2022
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.
- |||||||||| anti-PD-1 antibody / Tikcro Technologies
Journal, PD(L)-1 Biomarker, IO biomarker: NASH limits anti-tumour surveillance in immunotherapy-treated HCC. (Pubmed Central) - Dec 16, 2021
When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH-HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8PD1CXCR6, TOX, and TNF T cells...Collectively, these data show that non-viral HCC, and particularly NASH-HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment.
- |||||||||| anti-PD-1 antibody / Tikcro Technologies
Characterization of molecular and spatial diversity of macrophages in hepatocellular carcinoma (Poster Hall) - Oct 1, 2021 - Abstract #SITC2021SITC_528;
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
- |||||||||| anti-PD-1 antibody / Tikcro Technologies
[VIRTUAL] Characterization of molecular and spatial diversity of macrophages in hepatocellular carcinoma (Channel 03) - Mar 11, 2021 - Abstract #AACR2021AACR_2729;
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.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), anti-PD-1 antibody / Tikcro Technologies
[VIRTUAL] The recently approved high-TMB criteria may introduce a sex bias in response to PD1 inhibitors (Channel 04) - Mar 11, 2021 - Abstract #AACR2021AACR_827;
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.
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