Research Highlight

Check out this abstract for some cool research Sophie Cressman from Ohio State University! She is in the middle of helping with using a mouse model to try and make pretreatment more effective for adoptive cell transfer therapies useful in human cancer treatment, HIV treatment, and CAR T-cell therapy. Pretty cool, huh?

Adoptive T-cell gene therapy, including Chimeric Antigen Receptor (CAR) T-cell therapy, is a new treatment method being investigated as a potential cure for certain cancers and other previously incurable diseases like HIV/AIDS. The efficacy of the therapy can be significantly improved by preconditioning patients before cell transplantation. During preconditioning, lymphodepletion treatment ablates lymphoid cells to create a favorable “space” for the transferred cells. Current lymphodepleting preconditioning methods, however, rely on high doses of toxic and non-specific chemotherapies which often result in variable therapeutic efficacy of CAR T-cells in patients and cause adverse and sometimes deadly side effects.

The general hypothesis is that CD3e-immunotoxin (CD3e-IT) treatment will work as a viable preconditioning method for T-cell gene therapy by depleting all organs’ T cells prior to adoptive T-cell transplant and promoting the survival then repopulation of transplanted T-cells. CD3e-IT, an anti-CD3e monoclonal antibody conjugated with diphtheria toxin, is a potentially safer and more effective preconditioning regimen for adoptive T-cell therapy. The Kim lab has recently developed a murine version of CD3e-IT using murine CD3e monoclonal antibody with Fc silencing mutations and, in a preliminary study, found that CD3e-IT can specifically and effectively ablate the majority of T-cells in all organs, except CXCR5+ follicular T-helper cells (Tfh). Tfh in germinal centers (GC) are especially important in HIV infection as they remain a reservoir for HIV such that viral infection can persist even after antiretroviral therapy. Tfh are also significant therapeutic targets for follicular lymphomas of GC origin including follicular lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and angioimmunoblastic T-cell lymphoma. The goal of this study is to enhance the safety and efficacy of adoptive T-cell gene therapy by finding lymphodepletion preconditioning treatment conditions that will safely and effectively ablate all T-cells in the body, including Tfh, to promote the survival and functionality of adoptively transferred T-cells.