- |||||||||| LungVax (autologous haptenized tumor cell vaccine) / AVAX Technologies
Journal, Tumor-specific neoantigens: Neoantigen-specific cytotoxic Tr1 CD4 T cells suppress cancer immunotherapy. (Pubmed Central) - Jul 26, 2024
Here, using vaccines containing MHC class I (MHC-I) neoantigens (neoAgs) and different doses of tumour-derived MHC-II neoAgs, we discovered that whereas the inclusion of vaccines with low doses of MHC-II-restricted peptides (LDVax) promoted tumour rejection, vaccines containing high doses of the same MHC-II neoAgs (HDVax) inhibited rejection...We then documented modalities to overcome this inhibition, specifically via anti-LILRB4 blockade, using a CD8-directed IL-2 mutein, or targeted loss of cDC2/monocytes. Collectively, these data show that cytotoxic Tr1 cells, which maintain peripheral tolerance, also inhibit antitumour responses and thereby function to impede immune control of cancer.
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High doses of MHC-II neoantigens in peptide cancer vaccines induce tumor-specific inhibitory cytolytic CD4+ T cells (Ground Level - Exhibit Hall C - San Diego) - Sep 27, 2023 - Abstract #SITC2023SITC_340;
Results Vaccines containing tumor specific MHC-I neoAgs plus low doses of MHC-II neoAg (LDVax) promote tumor rejection...A similar reprogramming occurred following genetic depletion of cDC2 or treatment with a novel cis-targeted IL-2 mutein (CD8-IL2) that selectively activates CD8+ T cells. 2 Conclusions These results provide a roadmap to improve efficacy of cancer vaccines and potentially other immunotherapies by circumventing the generation/function of a heretofore unrecognized inhibitory CD4+ T cell population.
- |||||||||| LungVax (autologous haptenized tumor cell vaccine) / AVAX Technologies
Enrollment change, Trial termination, Tumor cell: DNP-Modified Autologous Tumor Cell Vaccine for Resectable Non-Small Cell Lung Cancer (clinicaltrials.gov) - Dec 5, 2015
P1/2, N=6, Terminated,
2 Conclusions These results provide a roadmap to improve efficacy of cancer vaccines and potentially other immunotherapies by circumventing the generation/function of a heretofore unrecognized inhibitory CD4+ T cell population. N=42 --> 6 | Suspended --> Terminated; Suspended until capitalization is completed
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