We are proud to share the success of two early-career postdoctoral researchers at the Department of Oncology, Ahmet Hazini and Esther Ng, who have secured funding to deliver pioneering research projects that aim to advance the field of cancer immunotherapy.
Both scientists have received prestigious awards that enable early career researchers to acquire new skills, collaborate with experts, and emerge as leaders in their research field.
Ahmet Hazini - Developing CAR Macrophages as Targeted Prostate Cancer Vaccines
Ahmet Hazini, PhD, has been awarded the Prostate Cancer UK (PCUK) Career Acceleration Fellowship, a prestigious grant that provides early-career postdoctoral researchers with funding to pursue independent research goals and develop unique expertise in the field of prostate cancer research.
With this funding, Ahmet will undertake a research project focused on engineering tumour-associated macrophages (TAMs) to induce an anti-cancer immune response. The project, titled ‘Developing CAR Macrophages as Targeted Prostate Cancer Vaccines’, seeks to investigate cutting-edge immunotherapeutic treatment strategies for patients with prostate cancer.
TAMs are complex and dynamic cells with numerous pro-tumorigenic functions. They are abundant in the tumour microenvironment, playing a crucial role in creating an immunosuppressive ecosystem that impedes the action of many cancer treatments. Research has shown that these macrophages contribute to tumour progression, metastasis, and immune suppression. By reprogramming TAMs and engineering them to express a chimeric antigen receptor (CAR), Ahmet hopes to enhance their pro-inflammatory and antigen-presentation capabilities, thus enabling them to drive anti-cancer immune responses.
What caught my attention was the dual nature of macrophages. While they play a role in supporting tumour progression, they also have the ability to cross-present tumour antigens and naturally access the tumour microenvironment. Unlike T cells, which often face challenges in reaching tumours, macrophages are better suited to navigate these barriers. This intriguing balance encouraged me to explore their potential as therapeutic targets.’
CAR technology has revolutionised cancer immunotherapy by enabling the creation of immune cells directed towards specific tumour-associated antigens. By reprogramming a patients’ own immune cells, this active immunisation approach stimulates the immune system to recognise and attack specific tumour-associated antigens. While showing remarkable success in haematological malignancies, the application of CAR-T cell therapy in solid tumours remains a challenging issue. Limited infiltration of effector immune cells into the tumour microenvironment is a significant challenge. As they are actively trafficked into the TME in large numbers, the use of CAR-modified macrophages could overcome this issue.
“My goal is to develop innovative prostate cancer vaccines by engineering targeted macrophages that educate T-cells to recognize and attack both primary and metastatic prostate cancer cells. This approach aims to provide an effective treatment option for prostate cancer patients at every stage of the disease.”
Treatment-resistant disease recurrence remains a major challenge in prostate cancer management and patients with advanced and metastatic disease face poor prognoses. Ahmet will work with world-leading colleagues across Oxford and beyond to investigate the potential of CAR-macrophages as an innovative prostate cancer treatment approach.
“The funding from Prostate Cancer UK is invaluable in advancing my research and career, enabling the development of cutting-edge, personalized immune therapy for prostate cancer.”
Esther Ng - Understanding the pathophysiology of autoimmunity through immune checkpoint blockade
Esther Ng is a clinician scientist who has obtained a Wellcome Trust Early Career Award to undertake a project in the Fairfax lab, focused on the pathophysiology of autoimmunity through immune checkpoint blockade. The Wellcome Trust provides funding for early-career researchers to deliver innovative research projects that aim to advance understanding in the oncology field.
Immune checkpoint blockade is an immunotherapeutic approach that blocks checkpoint proteins on tumour cells from activating inhibitory immunoreceptors on immune cells, reinvigorating their anti-tumour function.
While the use of these agents has reshaped outcomes for many cancers, the common occurrence of autoimmune side effects, known as immune-related adverse events (irAEs), remains a significant issue. The determinants of irAEs are poorly understood, especially why divergent organ systems become involved in different patients. In her project, Esther will use data from the OxCITE cohort to explore the relationships between the patient T-cell receptor (TCR) repertoire, HLA, and the mutational signature of a cancer, and what impact these have on organ-specific irAEs.
“I am fascinated by the link between autoimmunity, cancer and infection and I believe that understanding the T- and B-cell repertoire is key to studying these closely related phenomenon.”
Specialising in computational immunology, Esther will build deep learning models to study how these interactions impact autoimmunity. A better understanding of the factors driving irAEs will help to risk-stratify patients based on their individual immune profile and tumour characteristics, as well as helping to discover new cancer neo-antigens and develop better cell-based therapies for cancer.
“I am passionate about using research to help patients. This award will enable me to translate research findings from bench to bedside and I am hugely grateful to the Wellcome Trust for this opportunity.”