Allogeneic CD4+ iNKT cellular immunotherapy promotes anti-tumoral T cell responses in a human B-lymphoma xenograft model
Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B583
Abstract ID: 5716
Presenting Author:
Dana C Baiu , Senior Scientist at Univ. of Wisconsin, Madison, Univ. of Wisconsin Sch. of Med. and Pub. Hlth.
Abstract:
iNKT cells are innate-like CD1d-restricted T cells that mediate potent anti-tumor responses in murine models and have shown therapeutic potential in clinical trials. In humans, expression of CD4 delineates two functionally distinct iNKT cell subsets, with CD4- iNKT cells mainly producing TH1 cytokines and showing cytolytic activity, while CD4+ iNKT cells display a polyfunctional phenotype and are linked to regulatory pathways. Here, we used an EBV-driven B-lymphoma model to investigate the anti-tumor effects of these two iNKT subsets. In a live cell imaging system, CD4- iNKT cells carried out cell-mediated cytotoxicity and limited tumor spheroid growth in vitro, while CD4+ iNKT cells showed little anti-tumor activity. However, in a xenograft model, the effects of the two subsets were reversed. CD4- iNKT cells had no impact on tumor mass, which was likely due to down-regulation of CD1d by lymphoma cells in vivo. In contrast, administering CD4+ iNKT cells to tumor-bearing mice led to rapid reduction in tumor mass. CD4+ iNKT cells activated the expression of multiple co-stimulatory ligands by DCs, and human T cells from mice given CD4+ iNKT cell immunotherapy had enhanced responses against EBV. These results show that allogeneic CD4+ iNKT cell immunotherapy leads to potent anti-tumor activity in vivo that does not require tumor cell CD1d expression, and instead is associated with adjuvant-like activity that enhances anti-tumor responses by endogenous T cells.
Allogeneic CD4+ iNKT cellular immunotherapy promotes anti-tumoral T cell responses in a human B-lymphoma xenograft model
Category
Poster and Podium (Block Symposium)