Bispecific, Or-Gate Chimeric Antigen Receptor Responsive To CD19 And CD20
SUMMARY
UCLA research have developed a CD19‐OR‐CD20 chimeric antigen receptor (CAR) that can trigger T‐cell activation upon detection of CD19 or CD20.
BACKGROUND
Conventional T‐cell therapy utilizes single‐input anti‐CD19 CAR-T cells. Multiple clinical trials have reported remarkable therapeutic efficacy of this therapy against acute and chronic B‐cell malignancies. Unfortunately, several patients in these trials were reported to have relapsed due to the emergence of CD19‐negative leukemia or lymphoma. There is a need for a therapy that these cancers cannot easily develop resistance to.
INNOVATION
This technology identifies a CD19‐OR‐CD20 CAR that can trigger T‐cell activation upon detection of CD19 or CD20. This construct can be generated using standard molecular techniques and could be a step forward from traditional single‐input anti‐CD19 CAR T cells. Cancer cells will be less likely to successfully escape from T-cell therapy due to the need to lose both CD19 and CD20 instead of CD19 only, and the probability of such double-mutations is significantly lower than that of a single mutation.
APPLICATIONS
- Acute and chronic B‐cell malignancies
- Cancer therapeutics
ADVANTAGES
- CD19‐OR‐CD20 CAR that triggers T‐cell activation upon detection of CD19 or CD20
- Generated using standard molecular techniques
- Cancer cells less likely to successfully escape from T-cell therapy
STATE OF DEVELOPMENT
This innovation has been developed and tested using primary human T cells. It has been shown to trigger T‐cell activation, cytokine production, and target-cell lysis in vitro. It has further been shown to efficiently eradicate established lymphoma in vivo. Specifically, it has been shown in a mouse xenograft model that human T cells expressing the CD19-OR-CD20 CAR effectively prevent cancer relapse caused by the emergence of CD19-negative tumors, whereas T cells expressing the conventional, single-input CD19 CAR remain vulnerable to such spontaneous antigen loss by tumor cells. An Investigational New Drug application is currently in preparation for a phase I clinical trial targeting non-Hodgkin lymphoma, chronic lymphocytic leukemia, and small lymphocytic lymphoma.