Volume 2 Supplement 3

Abstracts of the 29th Annual Scientific Meeting of the Society for Immunotherapy of Cancer (SITC)

Open Access

Selective killing of malignant B cells using T cells redirected against malignancy variant receptor

  • Chungyong Han1,
  • Sujung Sim1,
  • Kwang Hui Kim1,
  • Don Gil Lee1,
  • Ho Sik Oh1,
  • Sang Hyun Park1,
  • Sunhee Hwang1,
  • Won Young Kim1,
  • Sangeun Lee1,
  • Young Ho Kim1,
  • Beom Kyu Choi1,
  • Carl June2 and
  • Byoung Se Kwon1
Journal for ImmunoTherapy of Cancer20142(Suppl 3):P16

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

Published: 6 November 2014

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.

Authors’ Affiliations

(1)
National Cancer Center
(2)
University of Pennsylvania

Copyright

© Han et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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