Anti-CD80 Monoclonal antibody, clone 27-20B2 [APC]

Immune checkpoint inhibitors (ICIs) treatment is becoming a new hope for cancer treatment. However, most prostate cancer (PCa) patients do not benefit from it. In order to achieve the accuracy of ICIs treatment in PCa and reduce unnecessary costs for patients, we have analyzed the data from TCGA database to find a indicator that can assist the choice of treatment. By analyzing the data of PCa patients with TMB analysis and immune infiltration analysis, we found the expression of immune cells in different immune infiltration groups. Commonly used markers of ICIs, expressed on CD8(+)T cell, were highly expressed in the high immune group. Then we used the forimmune cytolytic activity (CYT) to determine its relationship with the target of ICIs treatment. Through the analysis of CYT score and the ligands of immune checkpoints, we found that there was a significant correlation between them. With the increase of CYT score, the expression of CD80/86, PD-L1/L2, TNFSF14, and LGALS9 also increased gradually. Similarly, CD8(+)T cells were significantly increased in the CYT high group compared with the CYT low group in PRAD. The present research provides novel insights into the immune microenvironment of PRAD and potential immunotherapies. The proposed CYT score is a clinically promising indicator that can serve as a marker to assist anti-PD-L1 or other ICIs treatment. At the same time, it also provides a basis for the selection of other immune checkpoint drugs.

Overcoming tolerance to tumor-associated antigens remains a hurdle for cancer vaccine-based immunotherapy. A strategy to enhance the anti-tumor immune response is the inclusion of adjuvants to cancer vaccine protocols. In this report, we generated and systematically screened over twenty gene-based molecular adjuvants composed of cytokines, chemokines, and T cell co-stimulators for the ability to increase anti-tumor antigen T cell immunity. We identified several robust adjuvants whose addition to vaccine formulations resulted in enhanced T cell responses targeting the cancer antigens STEAP1 and TERT. We further characterized direct T cell stimulation through CD80-Fc and indirect T cell targeting via the dendritic cell activator Flt3L-Fc. Mechanistically, intramuscular delivery of Flt3L-Fc into mice was associated with a significant increase in infiltration of dendritic cells at the site of administration and trafficking of activated dendritic cells to the draining lymph node. Gene expression analysis of the muscle tissue confirmed a significant up-regulation in genes associated with dendritic cell signaling. Addition of CD80-Fc to STEAP1 vaccine formulation mimicked the engagement provided by DCs and increased T cell responses to STEAP1 by 8-fold, significantly increasing the frequency of antigen-specific cells expressing IFN gamma, TNF alpha, and CD107a for both CD8(+) and CD4(+) T cells. CD80-Fc enhanced T cell responses to multiple tumor-associated antigens including Survivin and HPV, indicating its potential as a universal adjuvant for cancer vaccines. Together, the results of our study highlight the adjuvanting effect of T cell engagement either directly, CD80-Fc, or indirectly, Flt3L-Fc, for cancer vaccines.