CD20-bispecific antibodies improve response to CD19-CAR T cells in lymphoma in vitro and CLL in vivo models.

Relapse after anti-CD19 chimeric antigen receptor (CD19-CAR) occurs in a substantial proportion of patients with lymphoid malignancies. We assessed the potential benefits of co-administering CD20-targeting bispecific antibodies (CD20-BsAbs) with CD19-CAR T cells with the aim of enhancing immunotherapeutic efficacy. Addition of CD20-BsAbs to cocultures of CD19-CARs and primary samples of B-cell malignancies, comprising malignant B cells and endogenous T cells, significantly improved killing of malignant cells and enhanced the expansion of both endogenous T cells and CD19-CAR T cells. In an immunocompetent mouse model of chronic lymphocytic leukemia, relapse after initial treatment response frequently occurred after CD19-CAR T-cell monotherapy. Additional treatment with CD20-BsAbs significantly enhanced the treatment response and led to improved eradication of malignant cells. Higher efficacy was accompanied by improved T-cell expansion with CD20-BsAb administration and led to longer survival with 80% of the mice being cured with no detectable malignant cell population within 8 weeks of therapy initiation. Collectively, our in vitro and in vivo data demonstrate enhanced therapeutic efficacy of CD19-CAR T cells when combined with CD20-BsAbs in B-cell malignancies. Activation and proliferation of both infused CAR T cells and endogenous T cells may contribute to improved disease control.

Brinkmann BJ ，Floerchinger A ，Schniederjohann C ，Roider T ，Coelho M ，Mack N ，Bruch PM ，Liebers N ，Dötsch S ，Busch DH ，Schmitt M ，Neumann F ，Roessner PM ，Seiffert M ，Dietrich S ... -  《-》

CD20-CD19 Bispecific CAR T Cells for the Treatment of B-Cell Malignancies.

Martyniszyn A ，Krahl AC ，André MC ，Hombach AA ，Abken H ... -  《-》

A tandem CD19/CD20 CAR lentiviral vector drives on-target and off-target antigen modulation in leukemia cell lines.

Schneider D ，Xiong Y ，Wu D ，Nӧlle V ，Schmitz S ，Haso W ，Kaiser A ，Dropulic B ，Orentas RJ ... -  《Journal for ImmunoTherapy of Cancer》

Bispecific anti-CD20, anti-CD19 CAR T cells for relapsed B cell malignancies: a phase 1 dose escalation and expansion trial.

Shah NN ，Johnson BD ，Schneider D ，Zhu F ，Szabo A ，Keever-Taylor CA ，Krueger W ，Worden AA ，Kadan MJ ，Yim S ，Cunningham A ，Hamadani M ，Fenske TS ，Dropulić B ，Orentas R ，Hari P ... -  《-》

Loop CD20/CD19 CAR-T cells eradicate B-cell malignancies efficiently.

CD19 chimeric antigen receptor (CAR) T cells have shown robust efficacy in relapsed and refractory acute lymphoblastic leukemia (R/R ALL), but compromising result in chronic lymphoblastic leukemia (CLL) and non-Hodgkin's lymphoma (NHL). CD19 relapse and the lack of CAR-T cell persistence which result in treatment failure are considerable obstacles to overcome. CAR-T targeting CD20 is an option for salvaging CD19 CAR-T failure. Previous studies have established variant structures of bispecific CAR-T which could avoid antigen-loss and immune escape. Here, we constructed tandem and loop CAR structures targeting both CD19 and CD20 antigen. Bispecific CAR-T cells could eliminate either CD19 or CD20 negative lymphoma cells, suggesting they exhibited dual antigen targeting of CD19 and CD20. By comparing the efficiency of four bispecific CAR modified T cells, it was found that loop2019 CAR was the best structure among them to eradicate lymphoma cell lines and patients' primary lymphoma or CLL cells in a very low dose in vitro and prolong the survival time dramatically in lymphoma xenograft mice model. These data highlighted the potential of loop2019 CAR-T in clinical treatment.

Chen Z ，Liu Y ，Chen N ，Xing H ，Tian Z ，Tang K ，Rao Q ，Xu Y ，Wang Y ，Wang M ，Wang J ... -  《-》