Adenoviruses Show Promise in Treating B Cell Lymphoma

Strategic Insights -

Researchers in England have found that adenoviruses encoding CD40L or IL-2 are effective against B cell lymphoma. In their study, investigators infected A20 B lymphoma cells with a replication-defective adenovirus encoding murine CD40L, but not IL-2, and observed an antigen presentation phenotype with upregulation of MHC Class I/II, induction of B7-1/2 molecules, and production of IL-12 and MIP-1alpha. 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, while vaccination with Ad-mCD40L-infected A20 cells produced a significant delay in tumor growth and long-term survival.

Key Takeaways:

  • Adenoviruses encoding CD40L or IL-2 were effective against B cell lymphoma, with CD40L being the most effective against tumor growth and long-term survival.
  • Vaccination with irradiated Ad-mCD40L-infected A20 cells generated A20-specific CD8+ T cell responses and cross-reactive A20 Ig antibodies.
  • Combination 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 was the most effective method in generating protective immunity.
  • Significant A20-specific CD8+ T cell-mediated cytotoxicity was only demonstrated in splenocytes from vaccinated animals, while ELISPOT assay demonstrated increases in gamma-interferon release by T cells elicited by in vitro stimulation with A20 cells or another syngeneic 2PK-3 lymphoma.
  • Post-vaccination, A20 idiotype-specific and non-idiotype-specific anti-A20 immunoglobulin antibodies were generated.
  • 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, resulting in a significant long-term survival of 85% of tumor-bearing mice.

Statistics:

  • 85% of tumor-bearing mice showed significant long-term survival after treatment with the combination of Ad-mCD40L and Ad-mIL-2.
  • p=0.0039, indicating a significant delay in tumor growth and long-term survival after vaccination with Ad-mCD40L-infected A20 cells.
  • p=0.0027, p=0.0027, p=0.0163, indicating that combination priming with A20 cells infected with Ad-mCD40L, Ad-mIL-2, or their combination was the most effective method in generating protective immunity.

Sources:

  • Meziane, E. et al. (2004). Use of adenoviruses encoding CD40L or IL-2 against B cell lymphoma. Int J Cancer, 111(6), 910-920.
  • Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, Lancs, England. Email: pstern@picr.man.ac.uk.
  • Wiley-Liss, Division John Wiley & Sons Inc., 111 River Street, Hoboken, NJ 07030, USA.