Brad Nelson

Professor

Research Classification

Research Interests

Cancer immunology and immunotherapy
Cell Therapy of Cancer
Cell therapies
Clinical trials
Oncolytic viruses
T cell engineering

Relevant Thesis-Based Degree Programs

Affiliations to Research Centres, Institutes & Clusters

 
 

Research Methodology

I co-direct the BC Cancer Agency's Immunotherapy Program and oversee a GMP-compliant cell processing facility to support phase I clinical trials

Recruitment

Master's students
Doctoral students
Postdoctoral Fellows
Any time / year round
I support public scholarship, e.g. through the Public Scholars Initiative, and am available to supervise students and Postdocs interested in collaborating with external partners as part of their research.
I support experiential learning experiences, such as internships and work placements, for my graduate students and Postdocs.
I am interested in hiring Co-op students for research placements.

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ADVICE AND INSIGHTS FROM UBC FACULTY ON REACHING OUT TO SUPERVISORS

These videos contain some general advice from faculty across UBC on finding and reaching out to a potential thesis supervisor.

Graduate Student Supervision

Doctoral Student Supervision

Dissertations completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest dissertations.

Identfying and targeting immunogenic mutations in ovarian cancer (2016)

A hallmark of cancer is the accumulation of mutations, and a small proportion of these give rise to mutant neoantigens – mutated peptides bound to Major Histocompatibility Complex (MHC) and recognized by T cells. Accumulating evidence suggests that mutant neoantigens (hereafter referred to as “neoantigens”) underlie successful immune therapies in cancers with high mutation loads, such as melanoma. Moreover, neoantigen-specific vaccines have successfully targeted highly mutated murine tumor models. However, less is known about neoantigen-specific T cell responses in cancers with moderate mutation loads, such as ovarian cancer. I hypothesized that (1) modified peptide-based vaccination schedules can lead to enhanced antigen-specific T cell responses; (2) neoantigen-specific vaccines can elicit T cell responses that eradicate murine ovarian tumors; and (3) neoantigen-reactive T cells are detectable in human ovarian tumors and peripheral blood. To activate high frequencies of antigen-specific T cells, I developed a vaccination method involving repeated, daily immunizations with long peptides and adjuvant. This method elicited robust T cell responses that eliminated established murine tumors. I used these enhanced vaccination methods to target tumor-specific mutations identified by exome- and RNA-sequencing of the ovarian tumor model ID8-G7. Prophylactic and therapeutic vaccinations were performed targeting all expressed mutations that had a predicted MHCI binding affinity
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Master's Student Supervision

Theses completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest theses.

Immune infiltration in ovarian cancer and its significance in chemotherapy (2015)

High grade serous carcinoma (HGSC), the most commonly diagnosed ovarian cancer subtype, is often presented as late stage disease with high recurrence rates, thus contributing to poor prognosis. Despite poor survival outcomes, the presence of tumour-infiltrating lymphocytes (TIL) in primary, untreated tumours is associated with increased survival. However, little is known about the phenotype and composition of TIL subsets in HGSC patients following treatment. In this thesis, we investigated the functional phenotype of TIL and the changes in immune composition in tumours over the course of chemotherapy. In Chapter 2, we investigated the association of cytotoxic TIL with the presence of apoptotic tumour cells in primary tumours. By immunohistochemistry (IHC), we found that the majority of the CD8⁺T cells lack cytotoxic Ganzyme B and that the presence of both CD8⁺ and Granzyme B⁺TIL were not associated with the presence of apoptotic cleaved caspase-3⁺ tumour cells. In Chapter 3, we investigated the composition of TIL subsets in HGSC following neoadjuvant chemotherapy in matching pre- and post-chemotherapy tumour samples. By IHC, we found an increased density of intraepithelial T cells, CD20⁺B cells, and TIA-1⁺ and PD-1⁺TIL. In contrast, no significant change was found in the density of intraepithelial Granzyme B⁺TIL, FoxP3⁺T cells, or CD68⁺ macrophages. Patients with high CD8⁺TIL density following chemotherapy showed prolonged survival. Thus, we found the immune response to cancer is dynamic, and TIL populations change during the course of treatment. The results from this study indicate chemotherapy can alter the immunologic microenvironment in which tumour prior to chemotherapy lacking cytotoxic T cells can have increased infiltration of cytotoxic T cells and B cells, as well as PD-1⁺TIL. This study indicates the increased TIL infiltration following chemotherapy could be further enhanced with immunotherapies, such as tumour-specific vaccines and immune modulators (PD-1 blockade), to eradicate remaining tumour cells and reduce recurrences in HGSC. This work contributes to a better understanding of the effects of chemotherapy on TIL and this can lead to a more strategic development of immunotherapies in order to harness the anti-tumour immune response and mitigate immunosuppression against cancer.

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