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Autologous Vaccine and Adoptive Cellular Immunotherapy as Treatment for Brain Tumors

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Brain Tumor Immunotherapy

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Abstract

This chapter discusses a process that combines vaccination to induce an immune response (IR) against autologous tumor-associated antigens (TAAs) with adoptive transfer of autologous cancer Ag-specific effector T-lymphocytes to treat individuals with progressing cancer. The use of this approach for the treatment of brain malignancy is described. The rationale is that the multiple genetic defects accumulating in cells during malignant transformation and subsequent tumor growth lead to production of altered protein molecules that confer immunogenicity. The host immune system can recognize malignant cells as nonself. Vaccination with autologous cancer cells and an immunologic adjuvant primes T-lymphocytes against cancer Ags, and overcomes the Ag presentation defect that prevents malignancies from being recognized during their natural progression. Cancer Ags and nonspecific Ag receptor stimuli (such as anti-CD3) can activate primed T-lymphocytes to differentiate into Ag-specific effector cells in vitro, and interleukin-2 (IL-2) stimulates these cells to proliferate. Activated effector T-lymphocytes are able to travel to sites of tumor growth, enter and reject the tumor, and potentially cure tumor-bearing animals after being infused into the blood stream. This strategy has been used to cure several types of experimental gliomas, demonstrating that immune privilege, immune suppression, the blood-brain barrier (BBB), Ag presentation defects, and other theoretical barriers to successful IT can be overcome. Phase I/II clinical trials using patients with recurrent malignant astrocytoma have demonstrated that cancer Ag and adoptive transfer (AT) IT is feasible, minimally toxic, and potentially efficacious. The data justify further clinical trials of cancer Ag and AT in humans with central nervous system malignancies.

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Authors
  1. Gary W. Wood PhD
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  2. Frank P. Holladay MD
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Editors and Affiliations

  1. School of Medicine, University of California at Los Angeles, CA, USA

    Linda M. Liau MD, PhD , Donald P. Becker MD  & Timothy F. Cloughesy MD ,  & 

  2. Department of Pathology and Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, NC, USA

    Darell D. Bigner MD, PhD

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© 2001 Springer Science+Business Media New York

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Wood, G.W., Holladay, F.P. (2001). Autologous Vaccine and Adoptive Cellular Immunotherapy as Treatment for Brain Tumors. In: Liau, L.M., Becker, D.P., Cloughesy, T.F., Bigner, D.D. (eds) Brain Tumor Immunotherapy. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-035-3_8

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  • DOI: https://doi.org/10.1007/978-1-59259-035-3_8

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-110-3

  • Online ISBN: 978-1-59259-035-3

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