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Poster Presentation
Selective killing of malignant B cells using T cells redirected against malignancy variant receptor
  1. Chungyong Han1,
  2. Sujung Sim1,
  3. Kwang Hui Kim1,
  4. Don Gil Lee1,
  5. Ho Sik Oh1,
  6. Sang Hyun Park1,
  7. Sunhee Hwang1,
  8. Won Young Kim1,
  9. Sangeun Lee1,
  10. Young Ho Kim1,
  11. Beom Kyu Choi1,
  12. Carl June2 and
  13. Byoung Se Kwon1
  1. Aff1 grid.410914.90000000406289810National Cancer Center Gyeonggi-do Republic Of Korea
  2. Aff2 grid.25879.310000000419368972University of Pennsylvania Philadelphia PA USA

https://doi.org/10.1186/2051-1426-2-S3-P16

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    Meeting abstracts

    Background

    Advances in gene-transfer system and in-depth understanding of immune mechanism have made the immunotherapy a powerful tool for fighting against cancers. Recent studies demonstrated a therapeutic potential of T cells with chimeric antigen receptor (CAR) targeting CD19 in refractory hematopoietic malignancies. At the same time, however, hence the CD19 targeting results in normal cell destruction such as B cell aplasia, a novel marker that specifically expressed in malignant B cells should be applied. In this study, we developed anti-malignancy variant receptor (MVR) mAb that exclusively bound to malignant B cells but not to normal B cells, and demonstrated that autologous T cells expressing CAR construct with anti-MVR scFv (MVR-CAR T cells) efficiently suppressed the outgrowth of malignant B cells in lymphoid organs.

    Results

    Malignant B cell-specific monoclonal antibody was isolated from the Balb/c mice immunized with Burkitt's lymphoma cell line, L3055. The antibody specifically recognized the established B lymphoma cell lines and malignant B cells derived from acute lymphoblastic leukemia, chronic lymphocytic leukemia, and diffuse large B cell lymphoma patients. Q-TOF analysis revealed that anti-MVR mAb recognized one of the CD74 variants that distinctively expressed in malignant B cells. We used anti-MVR mAb to generate CAR T cells for the rapid and efficient production of autologous T cells targeting malignant B cells. MVR-CAR T cells were generated by stimulating T cells with anti-CD2, CD3, CD28 Ab-coated beads and transducing MVR-CAR construct using lentiviral vector system. Autologous MVR-CAR T cells efficiently induced cytotoxicity against EBV-transformed LCLs but not against the normal CD19+ B cells in vitro. Furthermore, when the MVR-CAR T cells were adoptively transferred into immune-deficient RAG2-/-γc-/- mice into which LCLs were subcutaneously injected 3 weeks previously, they efficiently suppressed the outgrowth of metastasized LCLs in secondary lymphoid organs in vivo.

    Conclusions

    We developed anti-MVR mAb - a novel malignant B cell-specific antibody. Anti-MVR mAb recognized one of CD74 variants that exclusively expressed on malignant B cells. MVR-CAR T cells successfully induced LCL-specific cytotoxicity in vitro and in vivo. Considering the unique specificity on malignant B cells, anti-MVR mAb can be a therapeutic of B cell malignancies without normal B cell destruction.