Embracing Diversity To Advance Science and Clinical Care

Diversity is a biological constant, beginning with DNA and how it’s expressed. The genetic code evolved to change, reliably picking up new mutations that can confer survival advantages or sometimes drive disease. All the variations we see in humanity stem from this one core feature.

And variation is central to many biological mechanisms, including adaptive immunity. T cells and B cells derive their strength from their heterogeneity, allowing them to fight off pathogens and other invaders.

The more we learn about immune biology, the more we appreciate how biological diversity confers strength. Recent research has shown that diverse T-cell receptors inside tumors can produce better outcomes. In other words, diverse immune responses establish the equilibrium to restrain disease.

This underscores why variation is a powerful force in biology – it’s incredibly effective. Diversity at the molecular, cellular and tissue levels allow organisms to adapt to challenging environments. On a human level, we embrace inclusion because, morally and ethically, it’s the right thing to do. However, we shouldn’t even have to go that far. Diversity works.

Where diversity is winning

When first proposed, the idea that we could harness the immune system to destroy cancer was novel, even heretical. Now, checkpoint inhibitors save countless lives and constitute a multi-billion-dollar industry.

These were later joined by CAR T-cell therapies, which have, in a short time, developed a large footprint in oncology. T cells are just the beginning. Researchers are now repositioning their work to truly harness immune cell diversity – NK cells, macrophages, and others – to fight cancer in even more exciting ways. Cell engineering has become a critical tool to harness immune cell diversity more productively to benefit patients.

These advances are expanding our horizons well beyond cancer. As our abilities to engineer diverse cells improve, we can begin to tackle autoimmune conditions, sickle cell disease, neurodegeneration and many other intractable conditions.

Where we have more work to do

There’s an urgent need to create more and better cell models to study cancer and other diseases. HeLa cells have been the go-to for several decades because they’re easy to work with and access. Unfortunately, that ease comes at a cost. Studying HeLa cells, or any single cell line, may not provide the most precise results for all indications. Newly engineered patient-derived tumor cell lines are necessary and welcomed. Developing new and robust cell models will not be easy, but choosing diversity often means taking a more difficult path.

In addition, as we diversify treatments, we must always consider how they will be deployed. CAR T-cell therapies are potential lifesavers, but patients can have difficulty accessing them. Because these bespoke treatments are exceptionally complex to produce, there are only around 130 hospitals in the United States that offer them, and some people must travel hundreds of miles for care. Even if insurance pays medical costs, the travel alone can take families to the economic breakpoint.

To democratize therapeutic access, we must establish off-the-shelf cell therapies for cancer and other diseases.

Another example is clinical trials. There’s a growing movement to diversify trials, but we must acknowledge there will be challenges. To diversify trials, researchers must engage with groups that justifiably mistrust the medical community. Overcoming this skepticism and capturing diverse cohorts is essential to capture valuable data that will help all communities.

There are other barriers to diverse trial recruitment. Few research institutions are based in and around predominantly Black neighborhoods, and distance could deter participation. In addition, criteria can be unnecessarily exclusionary, and some clinicians may have unconscious biases that stunt diverse recruitment.

Poor clinical trial diversity translates into fewer medical choices. We cannot afford these blind spots, and the Food & Drug Administration is taking notice, delivering new guidance on trial diversity in April 2022.

Fortunately, there are measures we can take to overcome these barriers. Thoughtful outreach to Black and other minority communities has proven successful. When institutions enter a community only to identify trial participants, that can seem predatory. However, building relationships through cancer screenings and other health-focused programs create a two-way dialogue that can lead to better participation.

Embracing the challenge

People are often torn between choosing the familiar or searching for more unique options, but creating novel approaches takes effort and entails risk. Diversifying clinical trials is difficult, but it’s the only way to produce the best, most actionable data. Developing new cell lines has its challenges, but we are long past the point when we can accept one-size-fits-all answers.

By engineering solutions that are scalable, global and supported by the best science, we have the potential to deliver more and better therapies for patients. But to get there, we need all stakeholders to collaborate, including pharma and biotech, CDMOs, regulatory agencies and cell engineering companies.

There’s no doubt that taking diverse paths is challenging. However, the alternative is leaving good ideas and solutions on the table, and we just can’t do that. We owe patients our maximum effort.

About the authors

Cenk Sumen, PhD, is chief scientific officer at MaxCyte®.

Tiffany King Peoples, PhD, is field application scientist at MaxCyte®.