Could vaccines soon be added to the ‘collective arsenal’ against cancer?

The emergence of PD-(L1) treatments has provided patients options where previously none existed, and the leading forms of these therapies have gone on to blockbuster sales. Ben Hargreaves finds that the next step to enhance these treatments further could be to find synergies with emerging therapies employing similar modes of action, such as therapeutic cancer vaccines.

Cancer treatment has seen a number of breakthroughs in recent years, whether through checkpoint inhibitor therapies, CAR-T therapies, or in the growing number of approvals of antibody drug conjugates. One area that is becoming more widely discussed with the potential to be added to this group is that of therapeutic cancer vaccines.

Unlike traditional vaccines, the new generation of cancer vaccines are delivered to patients who already have cancer cells. The principal is much the same as in checkpoint inhibitor treatment: preventing the cancer cells from evading detection by the body’s immune system and highlighting them for destruction by T cells.

The science around the area has existed for a long time. However, it is only with recent advances in the scientific community’s knowledge of the immune suppressive mechanisms that cancer cells employ that has allowed the technology behind cancer vaccines to develop rapidly. Previous generations of such treatments struggled, due to their inability to mimic the natural functions of the immune system, resulting in trials that failed once they extended beyond animal models. There are encouraging signs that the latest generation of therapeutic cancer vaccines may be able to see greater success.

Diverse approaches

The difficulty in treating cancer is that cancer cells can mutate to evade the immune system, such as by producing molecules that inhibit immune cells like CD-8 T cells and NK cells that would usually destroy them. The ability for cancer cells to create this suppressive tumour microenvironment (TME) allows them to avoid detection by the immune system. This is where cancer vaccines can be effective in allowing the immune system to ‘see’ past the suppressive elements of the TME and to destroy the cancer cells.

Pharmaphorum spoke to three biotechs that are all working in the area, to learn why the technology holds such potential and what is unique about their approach. IMV Inc., IO Biotech, and PDC*line Pharma have all developed their own strategy and have assets progressing through phase I to III trials.

IMV possesses a proprietary ‘no-release’ lipid-based delivery platform, which could offer advantages over traditional formulations, evading issues of the delivery cargo ‘leaching’ into other tissue.

IO Biotech uses pre-existing T cells to reduce or eliminate immunosuppressive processes in the TME, with the technology able to simultaneously target multiple mechanisms without a significant increase in toxicity.

PDC*line is utilising specific plasmacytoid dendritic cells (PDCs) that play a role in priming and expanding cytotoxic T cells.CEO, Eric Halioua, explained that dendritic cells are considered the ‘most potent’ therapeutic vaccines approach “due to their unique antigen-presenting properties.”

He expanded to say, “PDC*line is much more potent than conventional DCs in priming and boosting fully functional antitumor CD8+ T cells, displaying a strong cytotoxic activity against tumour cells. Contrary to autologous DC-based vaccines, it is an off-the-shelf approach, easily scalable at industrial scale.”

Better together

Another advantage that Halioua raised is one that many are looking at: the synergy between cancer vaccines and current checkpoint inhibitor treatments. As new and effective innovations emerge, particularly in an area of acute need, such as oncology, the financial rewards for such treatments are rich.

An example of this is Merck’s Keytruda (pembrolizumab), a PD-1 checkpoint inhibitor that brought in full year 2021 sales of $17.2 billion. With revenues for the most effective treatments being so high, there is incentive to invest in emerging technologies to bolster the outcomes or the range of targets of such products.

Both IMV and IO biotech are partnered with Merck on a combination trial for their pipeline candidates alongside Keytruda. Jeremy Graff, chief scientific officer at IMV, stated, “The discovery and advancement of checkpoint inhibitors has played a major role in immunotherapy treatment, since tumours often leverage the checkpoint inhibition pathway [in order] to remain unnoticed and escape recognition from the immune system. Combining checkpoint inhibitors with cancer vaccines can offer a potentially well-rounded treatment to both attack cancer and limit its escape mechanisms from all sides.”

When talking specifically on IMV’s capabilities, he noted that the company’s vaccine candidates had shown ‘synergistic effect’ alongside checkpoint inhibitors, as well as ‘other treatment’ with different mechanisms of action.

Similarly, chief scientific officer at IO Biotech, Muhammad Al-Hajj, told pharmaphorum, “The TME vaccines we’re developing could be the cornerstone for successful T-cell based therapies, since they can fine tune the condition of the tumour to a more permissive state, allowing a complementary potent immune therapy to realize its full therapeutic potential. “

Al-Hajj continued to say that because of the features of its vaccine approach, it could work with a range of modalities, whether those be cell therapies, bispecific antibodies, or any treatment that could be aided by a microenvironment modulating agent.

Closing in on a first approval

There are still no approved therapeutic cancer vaccines. However, clinical trials are bringing vaccine candidates closer than ever to the point of validation and approval. IO Biotech is currently taking its lead candidate, IO102-IO103, into phase III clinical trials for melanoma in combination with Keytruda. IMV’s lead asset is maveropepimut-S (MVP-S), which has advanced into phase II trials in combination with Keytruda in diffuse large B cell lymphoma and is at the same stage as a monotherapy being trialled against ovarian cancer.

For PDC*line, it is currently taking its lead candidate for non-small-cell lung cancer through phase I/II trials, with and without anti-PD-1. The company expects the final report from the trial in the second quarter of 2024, at which point it plans to conduct a phase II/III study. Further than this, PDC*line will explore other indications for the candidate in phase II, such as in head and neck cancer.

Immune-checkpoint inhibitors, such as anti-PD-(L)1 treatments, have changed the face of cancer treatment over recent years. They have provided treatment where previously there were no further options. Halioua outlined the potential importance of therapeutic cancer vaccines to extend these gains even further, by noting that approximately 70% of patients do not yet respond to these treatments.

“Non-responders often lack pre-existing anti-tumour immunity. Therefore, a combination with therapeutic vaccines is expected to improve the response to anti-PD-(L)1 immune checkpoint inhibitors,” Halioua said. Such comments were echoed by Al-Hajj, who told pharmaphorum that he expects vaccines to become one element in the ‘collective arsenal’ needed to tackle tumour indications.