Immunotherapy Achievements, Awards, & Prizes

• Research Home
>
• Laboratory Research
>
• Cancer Immunology Program
>
• Immunotherapy
>
• Immunotherapy Achievements, Awards, & Prizes

Immunotherapy Achievements, Awards, & Prizes - Research at Peter Mac

Dr Phil Darcy

National Health and Medical Research Council (NHMRC) Career Development Award (CDA2), 2004–08.

Michael Kershaw

Peter MacCallum Cancer Center Junior Investigator Award, $100,000 p.a, 2006–09.

Maria Moeller

ASI International Postdoctoral Travel Award, 2008. CASS Foundation International Travel Award, 2008.

Hollie Pegram

ASI International Postgraduate Travel Award, 2008.

Sally Amos

Jomar Biosciences Award for Outstanding Presentation, IgV conference, Beechworth, 2008.

Recent Research Achievements

TOLL-LIKE RECEPTOR TRIGGERING AND T CELL COSTIMULATION INDUCE POTENT ANTI-TUMOR IMMUNITY IN MICE. To simultaneously direct multiple immune components against cancer we combined the Toll-like receptor agonist CpG 1826 with a T cell costimulatory antibody specific for CD137. This combination was demonstrated to eradicate established malignancies in mice. Crucial roles for CD8+ T cells, NK cells and interferons were demonstrated. CpG and anti-CD137 injection led to activation of dendritic cells and optimal expansion of activated T cells in the blood. Gene expression analysis revealed that CpG upregulated a variety of genes, with those associated with macrophage biology being particularly well represented, but subsequent studies demonstrated that depletion of macrophages in vivo led to an enhancement of therapy, which has not been previously reported. Long-term surviving mice were resistant to tumor rechallenge, demonstrating immunological memory. In addition, we demonstrate, for the first time, that mice lacking B cells have a total loss of a recall response against tumor, suggesting a role for B cells in the induction of anti-tumor immunological memory. This study provides support for the use of combination treatments stimulating multiple facets of immunity for the effective immunotherapy of cancer. COMBINING ADOPTIVE IMMUNOTHERAPY WITH TOLL-LIKE RECEPTOR (TLR) AGONISTS FOR THE TREATMENT OF MELANOMA IN MICE. Adoptive immunotherapy is showing great promise for the treatment of melanoma although current treatment regimens are associated with significant side effects, and tumour regressions are not always long lasting. In attempts to enhance adoptive immunotherapy, we have combined T cell transfer with intratumoural injection of TLR agonists that mimic infection. We have shown that approximately 20% of mice can achieve long-term regression of established melanoma using this therapy. In addition, we have demonstrated that interferon produced by the transferred T cells plays a crucial role in the anti-tumour effects. ADOPTIVE TRANSFER OF GENE-MODIFIED PRIMARY NK CELLS CAN SPECIFICALLY INHIBIT TUMOUR PROGRESSION IN VIVO. Natural Killer (NK) cells hold great potential for improving the immunotherapy of cancer. Nevertheless, tumor cells can effectively escape NK cell mediated apoptosis through interaction of MHC molecules with NK cell inhibitory receptors. Thus, to harness NK cell effector function against tumors, we employed Amaxa gene transfer technology to gene-modify primary mouse NK cells with a chimeric single chain (scFv) receptor specific for the human erbB2 tumor-associated antigen. The chimeric receptor was composed of the extracellular scFv anti-erbB2 antibody linked to the transmembrane and cytoplasmic CD28 and TCR-ζ signaling domains (scFv-CD28-ζ). In this study we demonstrated that mouse NK cells gene-modified with this chimera could specifically mediate enhanced killing of an erbB2+ MHC class I+ lymphoma in a perforin-dependent manner. Expression of the chimera did not interfere with NK cell-mediated cytotoxicity mediated by endogenous NK receptors. Furthermore, adoptive transfer of gene-modified NK cells significantly enhanced the survival of RAG mice bearing established intraperitoneal RMA-erbB2+ lymphoma. In summary, this data suggests that utilization of genetically modified NK cells could broaden the scope of cancer immunotherapy for patients.