Cell-based vaccines for the stimulation of immunity to metastatic cancers

Suzanne Ostrand-Rosenberg, Beth A. Pulaski, Virginia K. Clements, Ling Qi, Matthew R. Pipeling, Laura Hanyok

Research output: Contribution to journalArticle

Abstract

We are developing vaccines for inducing immunity to metastatic cancers. Although primary tumors are frequently cured by surgery, chemotherapy, or radiation therapy, metastatic lesions often do not respond to these treatments or proliferate after conventional therapy is terminated. Vaccine therapy for established metastases as well as prophylactic vaccine treatment to prevent outgrowth of latent metastatic tumor cells would therefore be beneficial. Our goal is to activate CD4+ and CD8+ T lymphocytes; however, we have focused on activating tumor-specific CD4+ T-helper lymphocytes because of their pivotal role as regulatory cells and in the generation of long-term immunological memory. The vaccines are based on the premise that tumor cells express potentially immunogenic antigens that could be targeted for T-cell activation, and that if appropriately genetically modified, tumor cells could be antigen presenting cells for these antigens. To facilitate direct antigen presentation to CD4+ T cells, tumor cells have been transfected with syngeneic major histocompatibility complex class II, co-stimulatory molecule, and/or superantigen genes. In vivo studies in three mouse tumor models demonstrate that vaccination protects against future challenge with wild-type tumor, cures some solid primary tumors, reduces established metastatic disease, and extends mean survival time. Antigen presentation studies demonstrate that in vivo vaccine efficacy is directly related to in vitro antigen presentation activity. The relevance of antigen presentation activity of the vaccines is further confirmed by in vivo studies demonstrating that during the immunization process, the vaccines directly present tumor-encoded antigens to CD4+ T lymphocytes. Adaptation of these vaccines for the treatment of human metastatic cancers is discussed.

Original languageEnglish (US)
Pages (from-to)101-114
Number of pages14
JournalImmunological Reviews
Volume170
DOIs
StatePublished - 1999
Externally publishedYes

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Immunity
Vaccines
Neoplasms
Antigen Presentation
T-Lymphocytes
Immunologic Memory
Antigens
Active Immunotherapy
Superantigens
Long-Term Memory
Neoplasm Antigens
Antigen-Presenting Cells
Therapeutics
Helper-Inducer T-Lymphocytes
Major Histocompatibility Complex
Immunization
Vaccination
Radiotherapy
Neoplasm Metastasis
Drug Therapy

ASJC Scopus subject areas

  • Immunology

Cite this

Ostrand-Rosenberg, S., Pulaski, B. A., Clements, V. K., Qi, L., Pipeling, M. R., & Hanyok, L. (1999). Cell-based vaccines for the stimulation of immunity to metastatic cancers. Immunological Reviews, 170, 101-114. https://doi.org/10.1111/j.1600-065X.1999.tb01332.x

Cell-based vaccines for the stimulation of immunity to metastatic cancers. / Ostrand-Rosenberg, Suzanne; Pulaski, Beth A.; Clements, Virginia K.; Qi, Ling; Pipeling, Matthew R.; Hanyok, Laura.

In: Immunological Reviews, Vol. 170, 1999, p. 101-114.

Research output: Contribution to journalArticle

Ostrand-Rosenberg, S, Pulaski, BA, Clements, VK, Qi, L, Pipeling, MR & Hanyok, L 1999, 'Cell-based vaccines for the stimulation of immunity to metastatic cancers', Immunological Reviews, vol. 170, pp. 101-114. https://doi.org/10.1111/j.1600-065X.1999.tb01332.x
Ostrand-Rosenberg, Suzanne ; Pulaski, Beth A. ; Clements, Virginia K. ; Qi, Ling ; Pipeling, Matthew R. ; Hanyok, Laura. / Cell-based vaccines for the stimulation of immunity to metastatic cancers. In: Immunological Reviews. 1999 ; Vol. 170. pp. 101-114.
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