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Use of adenoviruses encoding CD40L or IL‐2 against B cell lymphoma
Author(s) -
Meziane El Kahina,
Bhattacharyya Tapan,
Armstrong Anne C.,
Qian Cheng,
Hawkins Robert E.,
Stern Peter L.,
Dermime Said
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20332
Subject(s) - elispot , priming (agriculture) , immunology , cd8 , cd40 , biology , t cell , antibody , antigen , immune system , b cell , cytotoxic t cell , virology , in vitro , biochemistry , botany , germination
Some B cell lymphomas lack important costimulatory properties that could prevent them from being used as cell based vaccines. Infection of A20 B lymphoma cells with a replication‐defective adenovirus encoding murine (m) CD40L, but not mIL‐2, produces an antigen presentation phenotype with upregulation of MHC Class I/II, induction of B7‐1/2 molecules and production of MIL‐12 and MIP‐1α. Subcutaneous vaccination with irradiated Ad‐ mCD40L ‐infected‐ or Ad‐ mIL‐2 ‐infected‐A20 cells generated A20‐specific CD8 + T cell responses and cross reactive A20 Ig antibodies. Only vaccination with Ad‐ mCD40L ‐infected A20 cells produced a significant delay in tumor growth and long‐term survival ( p = 0.0039). Stronger protective immunity to A20 challenge was generated by intravenous priming with A20 cells infected with Ad‐ mCD40L , Ad‐ mIL‐2 or their combination followed by a boost immunization with A20 cells activated with syngeneic fibroblasts expressing CD40L. Compared to Ad‐ LacZ ‐infected A20 priming, the combination priming was most effective followed by Ad‐ mCD40L and Ad‐ mIL‐2 ( p = 0.0027, p = 0.0027, p = 0.0163 respectively). Significant A20‐specific CD8 + T cell‐mediated cytotoxicity was only demonstrated in splenocytes from these groups of vaccinated animals. By contrast, ELISPOT assay of splenocytes from all A20 prime/boosted vaccinated groups demonstrated increases in γ‐interferon release by T cells elicited by in vitro stimulation either with A20 cells or another syngeneic 2PK‐3 lymphoma, indicating the presence of cross reactive immunity. Similarly anti‐A20 immunoglobulin antibodies generated after vaccination were not necessarily A20 idiotype‐specific. Direct therapy of pre‐established tumors was achieved with the combination of Ad‐ mCD40L and Ad‐mIL‐2 given at Days 4 and 8 at the tumor site with a significant long‐term survival of 85% of tumor‐bearing mice ( p = 0.0001). Our study strongly supports the use of Ad‐ CD40L and Ad‐ IL‐2 combination therapy for the treatment of patients with B cell lymphoma. © 2004 Wiley‐Liss, Inc.