T lymphocytes redirected against the κ light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells

Juan Vera, Barbara Savoldo, Stephane Vigouroux, Ettore Biagi, Martin Pule, Claudia Rossig, Jessie Wu, Helen E. Heslop, Cliona M. Rooney, Malcolm K. Brenner, Gianpietro Dotti

Research output: Contribution to journalArticle

200 Scopus citations

Abstract

There has been interest in generating T cells expressing chimeric artificial receptors (CARs) targeting CD19/CD20 antigens to treat B-cell lymphomas. If successful, however, this approach would likely impair humoral immunity because T cells may persist long-term. Most low-grade lymphoma and chronic lymphocytic leukemia (B-CLL) cells express monoclonal immunoglobulins carrying either κ or λ light chains. We, therefore, explored whether T lymphocytes could be genetically modified to target the tumor-associated light chain, sparing B lymphocytes expressing the reciprocal light chain, and consequently reduce impairment of humoral immunity. We found that T lymphocytes expressing the anti-κ light chain CAR showed cytotoxic activity against Igκ + tumor cell lines and B-CLL cells both in vitro and in vivo. We also found that the incorporation of the CD28 endodomain within the CAR enhanced the in vitro and in vivo expansion of transgenic T cells after tumor-associated antigen stimulation. Free Igκ + did not compromise the ability of redirected T lymphocytes to eliminate Igκ + tumors because these free immunoglobulins served to sustain proliferation of CAR-CD28 transgenic T cells. Thus, adoptive transfer of T lymphocytes targeting the appropriate light chain could be a useful immunotherapy approach to treat B-lymphocyte malignancies that clonally express immunoglobulin without entirely compromising humoral immunity.

Original languageEnglish (US)
Pages (from-to)3890-3897
Number of pages8
JournalBlood
Volume108
Issue number12
DOIs
StatePublished - Dec 1 2006

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'T lymphocytes redirected against the κ light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells'. Together they form a unique fingerprint.

Cite this