2023 cancer research highlights: Drug development at its best

Lu Rahman selects some of the year’s interesting and noteworthy advances in cancer research drug discovery and development. As always, a year within cancer drug discovery and development brings with it significant breakthroughs, and 2023 has been no exception. Figures from the Amercian Cancer Society1 state that “a little over 1.9 million new cancer cases are expected to be diagnosed in the US in 2023”. In the UK, according to Cancer Research UK, around 167,000 people die from cancer in the UK each year. Research into new drugs and therapeutics is on-going and is helping drive mortality rates down. According to the American Association of Cancer Research (AACR)2, research-driven advances in treatments have resulted in the decline in death rates for melanoma, leukaemia, and kidney cancer. The association notes that the death rate for chronic myeloid leukaemia (CML), declined by 70% between 1975 and 2020 and says that this progress can be attributed to groundbreaking basic research discoveries from the 1960s to the 1980s that “identified the mechanistic underpinnings of the disease and propelled the development of a cascade of new treatments for CML”. Research into new cancer drugs remain strong. Earlier this year the AACR Chemistry in Cancer Research working group organised a set of sessions which featured first disclosures of 12 novel cancer agents3. These included: Next-generation CRISPR/Cas9-engineered allogeneic (allo) CAR-T cells incorporating novel edits that increase potency and efficacy in the treatment of lymphoid and solid tumours; the discovery of ARV-766, an androgen receptor degrading PROTAC for the treatment of men with metastatic castration-resistant prostate cancer and an antibody drug conjugate targeting CLDN18.2 expressing cancers. CRISPR and brain cancer Meanwhile, elsewhere in the US, another exciting development – using CRISPR as a therapeutic approach – has possibilities for tackling brain cancer. Scientists have used CRISPR gene editing to target and rapidly destroy glioblastoma cells in an approach that could apply to other highly mutated cancers. Using a technique they’ve dubbed ‘cancer shredding’, the researchers at Gladstone Institutes, California, programmed CRISPR to zero-in on repeating DNA sequences present only in recurrent tumour cells – and then obliterate those cells by snipping away at them. Working with cell lines from a patient whose glioblastoma returned after prior treatments, the team used CRISPR to destroy the tumour cells while sparing healthy cells. In glioblastoma, as with many other highly recurrent cancers, tumour cells that escape treatment develop multiple genetic adaptations that allow them to proliferate. The Gladstone team realised that these mutated cells have a unique genetic signature that could be targeted. “We see CRISPR as a gateway to a new therapeutic approach that won’t be subject to the possibility of tumour cell escape,” says Christof Fellmann, who led the study at Gladston. “Cancer shredding could hold potential not only for glioblastoma, but possibly for other hypermutated tumours.” Using IgE to treat cancer In the UK, a Cancer Research UK-funded clinical trial has shown, for the first time, that a new class of antibody could benefit cancer patients whose existing treatments have stopped working. A Phase I clinical trial, sponsored and managed by Cancer Research UK’s Centre for Drug Development, tested whether a type of antibody called IgE could be used to treat cancer. The drug, MOv18 IgE (an anti-folate receptor alpha IgE antibody), was developed by researchers at King’s College London. Currently, all antibodies approved for the treatment of cancer belong to a class known as IgG. Compared with IgG, IgE offers potential for enhanced immune system targeting of and potency against tumours, providing a more powerful weapon against cancer cells. Results from the trial, published in Nature Communications by researchers from King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, found that MOv18 IgE was well-tolerated in the majority of patients and was able to shrink the tumour of a patient with ovarian cancer who had not responded to conventional therapy. With the safety of MOv18 IgE having been established in cancer patients, biotechnology company Epsilogen has licensed the drug and will continue its clinical development following this successful clinical trial. Dr Nigel Blackburn, Director of Cancer Research UK's Centre for Drug Development, says: "What's interesting about IgE is its involvement in our body's defence against parasites and the particularly powerful immune response it elicits. We hope that through further trials, we will see it successfully target cancer cells with the same voracity, opening up an entirely new treatment option for patients." Ovarian cancer breakthrough According the World Cancer Research Fund International, ovarian cancer is the eighth most common cancer in women worldwide and there were more than 313,000 new cases of this disease in 2020. Genelux Corporation, a late clinical-stage immuno- oncology company, recently announced that the US Food and Drug Administration (FDA) has granted Fast Track designation for the development of Olvi-Vec (olvimulogene nanivacirepvec) for the treatment of patients with platinum resistant/refractory ovarian cancer. Olvi-Vec is a proprietary, oncolytic vaccinia virus (a non-human pathogen utilised as a vaccine to eradicate smallpox), and is modified to increase its safety, tumour selectivity and therapeutic potential. Virus-mediated oncolysis results in immunogenic cell death and triggers immune activation and memory for long-term immunotherapy against cancer. Olvi-Vec has been administered to more than 150 patients in clinical studies. In these studies, Olvi-Vec was generally well tolerated and the data provided evidence of clinical benefit. “The Fast Track designation granted for Olvi-Vec underscores its potential to address unmet medical needs in ovarian cancer, a significant recognition as we continue to enrol our Phase III OnPrime study,” says Thomas Zindrick, President, Chairman and CEO of Genelux. “We eagerly anticipate ongoing engagement with the FDA as we progress in the development of this promising treatment.” DDW Volume 25 – Issue 1, Winter 2023/2024 References: https://www.cancer.org/content/ dam/cancer-org/research/cancer- facts-and-statistics/annual-cancer- facts-and-figures/2023/2023- cancer-facts-and-figures.pdf https://cancerprogressreport.aacr. org/progress/cpr23-contents/ cpr23-cancer-in-2023/#driving https://www.aacrmeetingnews. org/news/researchers-report-first- disclosures-of-12-novel-cancer- agents/ About the author Lu Rahman is Publishing Director of DDW. She has over 25 years’ experience in B2B journalism, ten of those being in life sciences. She was previously DDW’s Editor in Chief and previous roles include Head of Life Sciences Content.