There are many avenues that researchers can—and do—pursue in the hopes of finding treatments for a given disease, condition, or disorder. One of those avenues is the research of oncolytic viruses to treat cancer. 

 spoke with Boris Minev, president, medical and scientific affairs, Calidi Biotherapeutics, about how oncolytic viruses can be harnessed for use in treatments, how stem cells are utilized, how oncolytic viruses compare to other methods of treatment on the market today, and challenges encountered during development and manufacturing.

 Your company develops allogeneic therapeutics in which oncolytic viruses are housed within stem cells to treat cancer. To start, what are oncolytic viruses, and how do these viruses have the potential to be used to treat cancers?

: Oncolytic viruses selectively infect and multiply inside cancer cells. They use a variety of mechanisms to target and infect cells, which often involve recognizing a molecular marker of a cell’s uncontrolled growth or ability to evade homeostatic checks and balances. While oncolytic viruses occur in nature, many have been modified in the lab to carry specific mutations that make them target and kill cancer cells more effectively, which improves their safety profile and increases their therapeutic potential.

Oncolytic viruses have great potential to be harnessed to treat cancers because they replicate within tumor cells in a targeted fashion, leaving healthy cells unharmed. Oncolytic virus therapy is especially potent because it kills cancer cells in two ways. First, the oncolytic virus selectively infects and replicates within the cancer cells at the tumor site, causing them to burst. Second, this cellular debris and viral antigens activate the patient’s immune system, triggering it to seek and destroy cancer cells near and far from the tumor site. Thus, all cancer cells at the tumor site, circulating in the blood, and at distant metastases—and any tumor cells that arise in the future—are subject to thorough eradication by the immune system, which reduces the risk of recurrence. More importantly, the oncolytic virus therapies have a high therapeutic index due to the following features: minimal systemic toxicity, non-overlapping with the toxicity of standard of care drugs; non-overlapping mechanisms of action with the standard of care drugs, allowing effective treatment combinations; low probability of generating treatment resistance (not seen so far); and virus dose in targeted tumors increases over time, as opposed to classical drug pharmacokinetics where drug concentration decreases over time.

Read the full article in the Emerging Therapies 2022 eBook.

Pharmaceutical Technology, Pharmaceutical Technology Europe

When referring to this article, please cite it as M. Rivers, "Treating Cancer with Oncolytic Viruses," 

Articles

Research into oncolytic viruses potentiated by stem cells shows promise for treating cancer. 

Treating Cancer with Oncolytic Viruses

Medicines have existed since the beginning of time—from what nature provided to the evolution of modern science. There has been a rapid evolution of APIs over the years, driven by innovation with different therapeutic modalities, which, due to varying challenges, require manufacturers to continuously learn and optimize their design processes. From antibodies to viral vectors to messenger RNA (mRNA) to oligos, each modality comes with its own ecosystem for manufacturing that requires the flexibility to grow quickly.

It's not just about the molecule mRNA. It’s the right molecule at the right time. Thanks to the rapid development of mRNA vaccines for COVID-19, the industry now has the momentum to overcome the challenges to realize the enormous potential of this technology.

Long before COVID-19, a small group of dedicated scientists and researchers had been studying and advancing this technology for cancer and other diseases. It took more than 30 years to overcome obstacles, such as mRNA destruction by chemicals in the blood. Fortunately, for the pandemic, scientists figured out how to teach the immune system cells to consume mRNA without drastic immune reactions.

Now, innovation is accelerating the development of these therapeutics. With proven potential, the industry will see the creation of new molecules that will hopefully lead to improved treatments for patients. With these advancements come process challenges and the need to build resilient and flexible manufacturing strategies that can adapt to the changing needs in a nascent industry.

Scott Ripley is the general manager, nucleic acid, for Cytiva.

When referring to this article, please cite it as S. Ripley, " Accelerating the Development of mRNA Therapeutics," 

Manufacturing and processing challenges surrounding mRNA can be overcome in order to realize the true potential of a technology 30 years in the making.

Accelerating the Development of mRNA Therapeutics

There is a need for more universally accepted definitions and processes involving chain of identity and chain of custody documentation for raw materials used in cell and gene therapies. Although current good documentation practices exist and are enforced by regulatory bodies, there is a vast discrepancy in how these practices are implemented across the industry. The industry must take steps to improve documentation integrity and standardize to reduce risk. Until standardization occurs, it will be difficult to ensure a system for raw material documentation.

BioPharm International’s September 2022 Emerging Therapies 2022

Julie Tilbury is a collection network liaison at Be The Match BioTherapies.

, September 2022
September 2022
Pages: 14–16

When referring to this article, please cite it as J. Tilbury, “Real-Time Post-Apheresis Documentation Decreases Errors," 

Manufacturing

Document integrity is critical in the provision of raw materials for cell and gene therapy manufacturing.

Real-Time Post-Apheresis Documentation Decreases Errors

The complexity of messenger RNA (mRNA)-based therapeutics is evident in the lipid nanoparticles (LNPs) used to encapsulate fragile mRNA cargo. Size, composition, aggregation, surface charge, and structure of LNPs can all have significant effects on a therapeutic molecule’s success. Unlike small-molecule drugs or protein therapeutics, which are chemically or biologically synthesized, LNPs self-assemble during the mixing of their component ingredients. This article discusses the challenges of LNP characterization as well as the analytical techniques that have proven successful in optimizing their development.

Hanna Jankevics Jones, PhD, and Natalia Markova, PhD, are pharmaceutical segment marketing managers at Malvern Panalytical.

, September 2022
September 2022
Pages: 22–25

When referring to this article, please cite it as H.J. Jones and N. Markova, “Shining a Light on Lipid Nanoparticle Characterization," 

Analytics

Using an orthogonal approach to lipid nanoparticle analysis can increase the odds of project success.

Shining a Light on Lipid Nanoparticle Characterization

The field of cell and gene therapy has delivered personalized and, in some cases, curative therapeutics for various conditions including cancer and monogenetic disorders. Cell and gene therapies have been studied in various forms for decades, primarily in academia, and in recent years have gained traction in treating real-world conditions. The tide began to change in cell therapy about a decade ago with the treatment of the first patients with CTL-019, the first chimeric antigen receptor T cells (CAR-T) approved by FDA, now known as Kymriah, at the University of Pennsylvania to treat acute lymphoblastic leukemia (ALL). And in gene therapy, Zolgensma took center stage for its ability to provide children with certain forms of spinal muscular atrophy (SMA), many times lethal by age four, a potentially curative treatment.

As the pace of commercial approvals begins to gain steam, there are key questions about how to efficiently develop and, potentially more importantly, manufacture these therapeutics at a cost that balances revenue with affordability. It’s well known that cell and gene therapies are driving massive innovation in medicine. According to a report, the market for cell and gene therapies is expected to reach more than $36 billion by 2027, driven by the increasing number of clinical and commercial cellular and gene therapy products.

Matt Hewitt is executive director, Scientific Services Cell and Gene Therapy at Charles River.

When referring to this article, please cite it as M. Hewitt, “The Road to Personalized Medicine: Reimagining Drug Manufacturing,” 

BioPharm International Emerging Therapies

For cell and gene therapies to reach their full potential, changes in manufacturing must be explored.

The Road to Personalized Medicine: Reimagining Drug Manufacturing 

When attempting to gauge the future of emerging therapies, it’s important to also look to the past for clues on what may be lurking beyond the horizon. Knowledge of what FDA has approved in the past is instrumental not only in understanding the current regulatory landscape, but also in determining the types of therapies that are likely to be approved going forward.

Of the 16 novel molecular entities and therapeutic biological products that have been approved by FDA in 2022 at the time of this article’s writing, the three discussed in this article are all but one of the biologics (1). While this is a significant decrease from 2021, which saw four biologics approved in November and December alone, it is notable that novel approvals as a whole are down significantly; at this time last year, there were 35 total approvals (i.e. both new drug applications and biologic license applications) approved (2).

While there are many reasons why such a decrease can occur, including simple random chance, it nonetheless places greater emphasis on what therapies are getting through the approvals process. Examining the biologics that are getting through could provide a baseline for the requirements needed to get through future approval processes.

Grant Playter is the Assistant Editor for 

When referring to this article, please cite it as G. Playter, "Novel Therapies of 2022," 

Quality/Regulations

Looking back at the biologics and large molecule drugs approved by FDA in the past year can give us hints toward what will be approved in the future.

Novel Therapies of 2022

The life sciences industry is seeing a robust trend in biotech incubator spaces geared toward fostering the growth of new and emerging biotech startups. Incubators on a global scale are determined to grow life sciences innovation in tandem with economically developing local regions. In the United States and other countries, life science sectors around the world are invigorated by efforts on the part of various entities—including government, industry, and academia. Working collectively, these entities aim to foster the growth of burgeoning regional biopharmaceutical industries by providing biotech startups space, talent, funding, and resources.

Feliza Mirasol is the science editor for 

, September 2022
September 2022
Pages: 28–33

When referring to this article, please cite it as F. Mirasol, “Biotech Incubators Cultivate a Global Scene," 

BioBusiness

The growth of the biopharmaceuticals market is feeding back into economies and, in part, is driving the boom in life sciences and biotech ecosystems.