Foxp1 Targeting to Enhance Anti-Tumor T-Cell Activity

Clinical evidence indicates that T cells exert immune pressure against cancer progression. In fact, the immune system is capable of recognizing and attacking tumor cells. However, at advanced stages, tumor reactive T cells become non-reactive even though tumors continue to remain immunogenic. The mechanisms responsible for this immunosuppression are not well understood. Since many current and in development oncology therapeutics exert efficacy by elicitation or reactivation of protective immunity, it will be critical to develop strategies to overcome such T cells unresponsiveness and maximize the effectiveness of these treatments. Clearly, such combination therapies will greatly enhance clinical outcomes.

Dr. Conejo-Garcia and colleagues have discovered a mechanism underlying T cell unresponsiveness in cancer, driven by the upregulation of the transcription factor Forkhead box protein.

P1 (FoxP1) in all human ovarian and breast cancer specimens analyzed (1). FoxP1 expression was shown to suppress anti-tumor T cells from proliferating and upregulating Granzyme-B and interferon-γ in response to tumor antigens. This mechanism is independent of anergy (defective T cell priming) or exhaustion (sustained exposure to suboptimal antigen concentrations) status. Importantly, the researchers demonstrated that in vivo Foxp1-deficient lymphocytes induced rejection of incurable tumors and promoted protection against tumor rechallenge.

The inventors are currently combining methods for inhibition and/or downregulation of FoxP1 with next generation small molecule, biologics and cell-based cancer oncology therapeutics.

Issued and pending applications cover compositions and methods of use. US9226936; 14/395762.

We are actively seeking a licensing or research and development collaborator to work with us to advance our Foxp1 therapeutic targeting strategy forward.

1. Stephen et al. Immunity. 2014 41(3): 427-9. PMID: 25238097