Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anti-CD38 chimeric receptor in conjunction with rituximab on B-cell non-Hodgkin lymphoma.

Using artificial receptors, it is possible to redirect the specificity of immune cells to tumour-associated antigens, which is expected to provide a useful strategy for cancer immunotherapy. Given that B-cell non-Hodgkin lymphoma (B-NHL) cells invariably express CD19 and CD38, these antigens may be suitable molecular candidates for such immunotherapy. We transduced human peripheral T cells or a T-cell line with either anti-CD19-chimeric receptor (CAR) or anti-CD38-CAR, which contained an anti-CD19 or anti-CD38 antibody-derived single-chain variable domain respectively. Retroviral transduction led to anti-CD19-CAR or anti-CD38-CAR expression in T cells with high efficiency (>60%). The T cell line, Hut78, when transduced with anti-CD19-CAR or anti-CD38-CAR, exerted strong cytotoxicity against the B-NHL cell lines, HT and RL, and lymphoma cells isolated from patients. Interestingly, use of both CARs had an additive cytotoxic effect on HT cells in vitro. In conjunction with rituximab, human peripheral T cells expressing either anti-CD19-CAR or anti-CD38-CAR enhanced cytotoxicity against HT-luciferase cells in xenografted mice. Moreover, the synergistic tumour-suppressing activity was persistent in vivo for over 2 months. These results provide a powerful rationale for clinical testing of the combination of rituximab with autologous T cells carrying either CAR on aggressive or relapsed B-NHLs.

Mihara K ，Yanagihara K ，Takigahira M ，Kitanaka A ，Imai C ，Bhattacharyya J ，Kubo T ，Takei Y ，Yasunaga S ，Takihara Y ，Kimura A ... -  《-》

Activated T-cell-mediated immunotherapy with a chimeric receptor against CD38 in B-cell non-Hodgkin lymphoma.

Mihara K ，Yanagihara K ，Takigahira M ，Imai C ，Kitanaka A ，Takihara Y ，Kimura A ... -  《-》

CD28 costimulation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T cells.

Kowolik CM ，Topp MS ，Gonzalez S ，Pfeiffer T ，Olivares S ，Gonzalez N ，Smith DD ，Forman SJ ，Jensen MC ，Cooper LJ ... -  《CANCER RESEARCH》

Natural expression of the CD19 antigen impacts the long-term engraftment but not antitumor activity of CD19-specific engineered T cells.

Cheadle EJ ，Hawkins RE ，Batha H ，O'Neill AL ，Dovedi SJ ，Gilham DE ... -  《-》

Potent in vitro and in vivo activity of an Fc-engineered anti-CD19 monoclonal antibody against lymphoma and leukemia.

Horton HM ，Bernett MJ ，Pong E ，Peipp M ，Karki S ，Chu SY ，Richards JO ，Vostiar I ，Joyce PF ，Repp R ，Desjarlais JR ，Zhukovsky EA ... -  《-》