The Veatch lab studies T cells targeting tumor antigens in solid tumors with the goal of developing novel cellular therapies for treating cancer. 

CD4 T cells as tools to modify the tumor microenvironment

CD4 T cells can lead to tumor rejection through direct killing of tumor cells, and through interaction with antigen presenting cells to support cytotoxic CD8 T cells and to activate antitumor innate immunity.

CD4 T cells in human tumors

We have found that conventional CD4 T cells infiltrating human melanoma tumors include both tumor antigen specific cells and non-specific “bystanders” and that the tumor antigen specific cells have a unique transcriptional signature.  The presence of cells with this signature across patients of multiple cancer types is correlated with improved prognosis and an activated tumor microenvironment as measured by the number and activation of CD8 T cells, the activation of macrophages, and the number and maturation of B cells.  This has led to the hypothesis that CD4+ T cells targeting tumor antigens could be used to activate the tumor immune microenvironment and potentially benefit patients with solid tumors.

Modelling CD4 T cell therapy in mouse models

We are using murine models to study gain and loss of function approaches to increase the activation of immune cells by CD4 T cells, to increase their antitumor effects while minimizing toxicity.CD4 T cells in human tumors.

Preclinical testing of CD4 T cell therapy in humaninzed mouse models and clinical trials

We are identifying T cell receptors allowing CD4 T cells to target recurrent mutations in solid tumors, including common mutations in BRAF and EGFR.  We are testing human T cell therapy products in preclinical humanized mouse models that contain human immune and tumor cells, and plan to extend this approach to first in human clinical trials in patients with melanoma, lung cancer, and Merkel cell carcinoma.