Cancer vaccines: not only treating tumors, but preventing them too

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Gloved hand holding a syringe under the word vaccine
The COVID-19 pandemic has brought vaccines back into the drug development spotlight, and mRNA vaccines are stealing the show with sales of USD 54.4 billion in 2021 alone. Few know that the developers of the mRNA COVID-19 vaccines actually drew upon years of experience attempting to develop cancer vaccines. This approach goes back several decades, and although the field has to date seen limited success, it has nevertheless witnessed a renewed interests in recent years. We examine the latest trends in cancer vaccine development, and where the opportunities lie for the future of the industry.

Before receiving attention for its successful Sars-CoV-2 vaccine Comirnaty, the well-known German mRNA-focused firm BioNTech was a company dedicated to cancer vaccines. The significant revenues from Comirnaty are now actively being funneled back into this pipeline, to advance the company’s cancer vaccine programs (which now boast ten clinical-stage assets, spanning four Phase II programs and eight Phase I programs). On the other side of the pond, the other famed mRNA company Moderna is also making news in the oncology space, with the announcement in October 2022 that Merck agreed to exercise its USD 250 million option to co-develop and co-commercialize a personalized cancer vaccine with the company.

Boosting cancer treatments

The promise of cancer vaccines lies in their ability to not only treat extant tumors, but to train our own immune systems to recognize and eradicate cancerous cells before tumor establishment. Despite the failures of more than 150 clinical programs in the past decades, and less than 10 approved cancer vaccine products, the field has kept evolving and learning from its past. Aided by recent breakthroughs – including new scientific insights in immuno-oncology; technological advances, like state-of-the-art genetic screening and AI-prediction; and new modalities, such as mRNA and DNA technology ­– the field is poised for a comeback.

“The promise of cancer vaccines lies in their ability to not only treat extant tumors, but to train our own immune systems to recognize and eradicate cancerous cells before tumor establishment.” – Ethan Kuo

For the last few decades, cancer vaccine development has primarily focused on products acting as secondary immuno-oncology therapies to treat tumors not well-served by current treatments, either on their own or in combination with other cancer therapies. Most of BioNTech’s clinical pipeline of therapeutic cancer vaccines exemplifies this focus: vaccines combined with immune checkpoint inhibitors or adjuvants to help break through the natural resistance tumors have to immune attacks. In this format, cancer vaccines are however in direct competition with other (combinatorial) immuno-oncology therapies, both established and experimental, and the vaccines can at best be viewed as add-ons to checkpoint inhibitors.

Injecting new life into the field

Spurred by these limitations, we have started to witness a growing number of drug development programs in cancer vaccines for preventative use. There are two noticeable approaches emerging in the preventive cancer vaccine space: (1) preventing the re-establishment of tumors in patients where their tumor has been surgically removed, but they still have detectable tumor DNA in their blood, and (2) preventing cancer development in a selected group of cancer-free individuals who, according to genetic testing, are deemed to be at high risk of developing certain types of cancer.

The first approach towards preventing tumor re-establishment is exemplified by the latest Phase II study designs of Moderna’s mRNA-4157 program on melanoma, and BioNTech’s BNT122 program on colorectal cancer. Both companies are using an approach that combines two things: the latest technological advancements, which enable personalized mRNA vaccines (including fast bench-to-bedside capability and next-gen sequencing of circulating tumor DNA); and a clever trial setup, that allows cancer vaccines to deal with cancer cells before tumor establishment (hence bypassing the hostile tumor microenvironment). Both programs are also combining their cancer vaccines with Merck’s immune checkpoint inhibitor Keytruda in order to maximize efficacy.

“There is a noticeable lack of VC funding in this area, likely due to the unattractively long timelines associated with clinical development of preventive cancer vaccines.” – Ethan Kuo

The second emerging approach – delivering preventive cancer vaccines to specific groups of people – has been made possible thanks to our improved understanding of genetic risk factors contributing to cancer development. Two non-VC-backed clinical studies exemplify this trend. The first, announced in September, is Blackstone’s USD 55 million gift to the University of Pennsylvania to support testing of Inovio’s Phase II DNA cancer vaccine INO-5401 as a preventative for breast cancer in people carrying BRCA1 and BRCA2 mutations. The other is a clinical Phase I/II cancer vaccine developed by the US National Cancer Institute to prevent colon cancer in high-risk patients with Lynch Syndrome. While encouraging, there is a noticeable lack of VC funding in this area, likely due to the unattractively long timelines associated with clinical development of preventive cancer vaccines.

Funding future shots

Read this article to find out how V-Bio portfolio company Precirix is tackling tumors with camelid antibodies

Cancer vaccines have been riding the recent wave of progress in many scientific and technological areas such as mRNA technology, immune checkpoint inhibition, and precision diagnostics. Although the industry continues to focus on their use as a therapeutic modality, cancer vaccines aimed at preventing tumor (re)establishment after treatment are likely to have an even higher chance of success, in terms of both competition and mechanism of action. This approach is currently being spearheaded by the mRNA-market-leaders BioNTech and Moderna, but we might soon see more VC-backed companies following the same route with other modalities, types of antigens, and drug combinations. The jury is still out, as convincing clinical evidence remains to be delivered. The dependency on checkpoint inhibitors also still needs to be evaluated, as it may detract in part from the benefit of cancer vaccines promised to patients, such as fewer side effects. Regarding the final approach – using vaccines to prevent tumor formation in people genetically at high risk of cancer – the field has to date found it challenging to raise VC funding. Unfortunately, as the approach holds huge potential for patients, the industry will likely require at least one successful example to draw on before investors can be convinced of the viability these types of projects.