University of Pittsburgh Cancer Institute (UPCI)

Immunobiology and Immunotherapy

Specific and potent immunotherapy, assisted by molecular targeting strategies, is a promising modality to recognize and destroy infiltrating cellular elements of brain tumors. For the development of clinically effective immunotherapy for brain tumors, current efforts are specifically directed to the following approaches:

1. identification of glioma-specific epitopes that can induce cytotoxic and helper T-cell immune responses
2. use of peripherally administered tumor vaccines to induce effective, systemic immune responses
3. delivery of immune effector cells to the target tumor sites while maintaining the activity of the effector cells, using cell and/or cytokine gene transfer
4. evaluations of safety and efficacy of glioma vaccines in a series of clinical trials

Selected Publications

• The nonsteroidal anti-inflammatory COX-2 inhibitors acetylsalicylic acid (ASA) or celecoxib inhibit gliomagenesis by directly supporting systemic development of myeloid-derived suppressor cells and their accumulation in the tumor microenvironment, where they limit cytotoxic T lymphocytes infiltration (Fujita et.al., Cancer Res. 2011, 71:2664-74).
• The safety and immunogenicity of a novel vaccination was evaluated in a clinical trial with α-type 1 polarized dendritic cells loaded with synthetic peptides for glioma-associated antigen epitopes and administration of polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant gliomas. For at least 12 months, nine patients achieved progression-free status, and one patient with recurrent GBM had a sustained complete response (Okada et.al., J Clin Oncol. 2011, 29:330-6).
• The RNase III endonuclease Dicer plays a key role in generation of microRNAs (miRs). Our findings show that Dicer is responsible for the generation of the mature miR-222 and -339, which suppress ICAM-1 expression on tumor cells, thereby down-regulating the susceptibility of tumor cells to CTL-mediated cytolysis. This study suggests potential clinical utility of novel miR-targeted therapies to promote cytolysis of tumor cells. (Ueda R, et. al. Proc Natl Acad Sci U S A. 2009 Jun 30;106(26):10746-51).

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