Illuminating The Innovation Behind A New Era Of Cancer Vaccines

By Life Science Connect Editorial Staff

Advancements in the pharma industry’s understanding of cancer and genome sequencing over the last several decades have led biotech companies to explore an exciting frontier in oncology treatment: cancer vaccines. New approaches that leverage improved technology and increased potency are driving the resurgence. At this exciting confluence, researchers are working to guarantee viability and efficacy for patients. “We're at a nexus now where we have enough of the biology to understand what's going on with cancer [to mount] an immune response against it,” notes President & Chief Technology Officer of Providence Therapeutics Robert Georgantas III, Ph.D. If developers skillfully navigate the manufacturing and regulatory landscape, the latest vaccine iterations have the potential to transcend the industry’s previous attempts and usher in a new era of treatment for cancer patients.

Why Now?

The answer is relatively straightforward: science and technology caught up to accommodate what researchers had long been attempting. Early iterations of cancer vaccines failed for a variety of reasons, including a collectively limited understanding of the immune system and antigen presentation as well as a lack of precision healthcare. With previous cancer vaccines, these shortcomings led to limited potency and efficacy. Additionally, developers often had to start with late-stage, immunocompromised patients whereas vaccines work best when tumors are small and early stage.

Now, with an increased understanding of how cancers invade the immune system and immune checkpoint inhibitors like PD-1, the landscape of cancer immunology has shifted toward vaccines becoming viable treatment options. Furthermore, technology has expanded to rapidly sequence and identify mutations, which has allowed researchers to improve targets. To ensure that a cancer vaccine is effective, developers must identify strong antigens, i.e., the molecules that bind to antibodies or T cell receptors and trigger an immune response. There are several factors that have been identified as components of an effective tumor antigen strategy, including triggering a broad immune response, targeting specific tumors, and pursuing multiple targets so that the cancer can’t escape.

Overall, vaccines are being considered as treatment options to use at the beginning of immunotherapy regimens and early in the disease phase. Some are even proposing the creation of preventive cancer vaccines that can be given to high-risk patients before cancer ever appears in the body. “When it comes to vaccines, I would say that one of the promises of immunotherapy and viral vaccine therapy is safety. Cancer is treated with some of the most extreme tools that medicine has – knives, radiation, and chemo. [These treatments] break down the patient's immune system. With the advancement of modern immunotherapies, the potential quality of life for the patient has [helped] change the way many people look at cancer and will look at a cancer diagnosis in the future,” notes HDT Bio’s Chief Scientific Officer Peter Berglund, Ph.D. At HDT, their AMPLIFY vaccine platform combines self-amplifying RNA with LION technology to treat both COVID-19 and cancer. Similarly, Providence Therapeutics developed a critical mRNA COVID-19 vaccine and is now looking to translate that platform into cancer vaccinations.

From a funding perspective, the answer is nuanced but optimistic. Overall, the pharma industry is experiencing a downturn in venture capital investment, yet the mRNA space continues to be an exciting prospect for investors. This is likely due to the post-COVID-19 mRNA wave. That said, Codagenix EVP for Oncology Johanna Kaufmann, Ph.D., clarifies that it isn’t that straightforward: “It is not easy going right now. Despite the billions of dollars invested in immunotherapy over the last 20 years, we haven't made the next big leap after the PD-L1 axis inhibition. This is an opportunity for us as scientists to convince the field that we know how to modulate the immunotherapy or tumor microenvironment better. We can work together to get out on the other side of this downfall.”

How Do Personal Cancer Vaccines And Off-the-Shelf Treatments Differ?

At Codagenix, they are leveraging modalities in which it isn’t necessary to know which mutations are antigenic based on sequencing. Per Kaufmann, “We are banking on the effect of viruses that essentially induce an in-situ vaccination effect, where through a mechanism called epitope spreading you recruit the right type of immune response to the cancer and let immunogenic cell death and other immunological mechanisms do their trick.” This strategy allows Codagenix to produce off-the-shelf products with faster availability and higher cost efficiency than modalities that require biopsy, sequencing, and customized manufacturing. Overall, these products afford patients greater equity and accessibility via the opportunity to be distributed outside of larger academic centers.

Personalized vaccine manufacturing is an alternate route. This technology requires a rapid biopsy to sequencing pipeline to treat patients proactively. Luckily, companies are now able to produce sequences in two to four weeks via advanced technologies. In the mRNA space, these are then synthesized and placed into a lipid nanoparticle (LNP). “We’re talking about turning around a personalized vaccine in one to two months, which is well within the treatment envelope of an aggressive cancer,” said Georgantas. However, in many cases, oncologic specialists are encouraging combined approaches, i.e., treating a patient with an off-the-shelf drug while a personalized vaccine is being developed.

What Do The Manufacturing & Regulatory Landscapes Look Like?

From a manufacturing perspective, developers are seeing both undercapacity and overcapacity. As the potential of the mRNA vaccine space grows, more and more contract development and manufacturing organizations (CDMOs) are joining the drug substance (DS) and drug product (DP) space, leading to overcapacity. Vaccine developers caution against trusting just any CDMO, though. “There are some CDMOs that are extremely good at this, but there are others claiming they do X, Y, and Z. They're new to the game and not experienced enough to produce a good product,” cautions Georgantas. Thus, the undercapacity is for experienced CDMOs.

To successfully manufacture these vaccines, CDMOs must leverage robust analytical techniques that ensure DS and DP are GMP quality, stable, and safe for patients. Flexibility is another appealing attribute in a manufacturing partner. For Kaufmann, her team is seeking expert partners that have the capacity for flexible small-scale production and experience with single-use systems. “There has been a lot of experience gained in the CDMO arena related to lentiviral vectors and adeno-associated viruses, but manufacturing [varied] types of viral species is a different ballgame. There are not enough CDMOs out there with the right type of expertise and [as a result, there are] relatively long lead times,” describes Kaufmann.

In terms of regulatory challenges, perhaps the largest is the relative novelty of cancer vaccines. For virotherapy, there is one FDA approved drug: T-VEC by Amgen, which is commercialized under the name Imlygic. Other biotechs looking to launch commercial virotherapies have the benefit of a proven pathway to FDA approval. mRNA cancer vaccines do not yet have an approval precedent to reference. Thus, navigating an approach to FDA approval may be unguided and, at times, difficult.

For improved outcomes, the experts recommend more collaboration. Per Kaufmann, “Let's work together to make this happen for patients. Let's not see each other as competitors but share our science to improve both biological understanding and technical aspects. We can make good on the promise of what this modality can do, whether that's prevention, prevention of recurrence, or therapeutic benefit.”

More Answers Await

As the immunology space expands to make vaccines a more viable cancer treatment option, developers are weighing their options and coming up with creative solutions to reach FDA approval and maximum efficacy for patients. By using cancer vaccines in concert with immunotherapies and other treatments, developers will expand the potential for patient care and, hopefully, spark a new wave of more effective cancer treatment plans.

The content of this article was originally presented in a live event hosted by Bioprocess Online Live host Matt Pillar, with guests Peter Berglund, Johanna Kaufmann, and Robert Georgantas. To listen to the full presentation, click here.