Principal Investigators at Saint John’s Cancer Institute, Kim Margolin, MD, and Przemyslaw Twardowski, MD, Discuss Immunotherapy Developments in Clinical Trials

What is the Future of Immunotherapy?

Advances in genomic profiling and biomarker discovery are leading towards personalized medicine. Tailoring treatments on individual tumor characteristics, genetic profiles, and immune system status is becoming more common as advances in research and innovative clinical trials continue.

Combining different immunotherapy agents (checkpoint inhibitors and cancer vaccines) or with traditional therapies (chemotherapy and radiation) is more common as individualized treatment plans emerge and a multi-disciplinary care approach becomes standard for cancer care. “We have what looks to be an exciting patient vaccine in melanoma in the adjuvant setting,’ explains Kim Margolin, MD, in the video below as she discusses new technology and clinical trials in immunotherapy.

Dr. Kim Margolin discusses immunotherapy and clinical trials
Dr. Kim Margolin discusses the benefit of combining immunotherapy agents.
Beyond PD-1, PD-L1, and CTLA-4 (cited in the video below), researchers at Saint John’s Cancer Institute are investigating new immune checkpoints and pathways that regulate immune response in the tumor microenvironment. Targeting these checkpoints could expand the spectrum of cancers that respond to immunotherapy and improve response rates.

Reducing toxicity and optimizing immunotherapy agents is ongoing.

“Sometimes in order to get those cytokines to be safe or effective, or to use them regionally… You have to really engineer them. So, you have to put them together in weird forms that are not found in nature, in order to enhance their activity or to mitigate their toxicities, and all of that is sort of a work in progress.”

– Kim Margolin, MD

What is the History of Immunotherapy?

Immunotherapy, as a concept, has a rich and evolving history, especially here at Saint John’s Cancer Institute (formerly the John Wayne Cancer Institute). In 1986, the FDA approved interleukin-2 for treating metastatic melanoma and renal cell carcinoma, marking a significant milestone in cancer immunotherapy. However, it was still highly toxic. Even so, the discovery of PD-1 and CTLA-4 led to the discovery of checkpoint inhibitors, which block signals and enhance the immune response against cancer cells.

Saint John’s Cancer Institute was founded by Dr. Donald L. Morton, a surgical and medical oncologist who pioneered immunotherapy and started T-cell research. “He was pursuing it in parallel with his MSLT-I and II surgical trials, with a different NIH-funded program project grant. Dr. Morton developed a cancer vaccine and had many phase I/II clinical trials at the cancer center, followed by international, multicenter trials for both Stage III and State IV melanoma…he was ahead of his time,” explains Lisa van Kreuningen, Administrative Director of Saint John’s Cancer Institute.

Today, this history and SJCI’s foundation in cancer immunotherapy and translational research has kept us at the forefront of personalized cancer care.

“At Saint John’s, we are doing several interesting trials.”

– Przemyslaw Twardowski, MD

Medical Oncologists in Melanoma and Renal Cell Carcinoma Discuss…

Kim Margolin, MD, and Przemyslaw Twardowski, MD, discuss immunotherapy at Saint John’s Cancer Institute.

Is Personalized Medicine Effective?

It can be more effective than standards of care when considering the biology of the tumor and the individual’s microenvironment.

Andy Luci was diagnosed with metastatic renal cell carcinoma and was treated by Dr. Przemyslaw Twardowski using a combination method of immunotherapy, and other checkpoint inhibitors. Learn more about the care approach and his amazing recovery.

Mike Antonson, a sergeant in the military, was diagnosed with metastatic melanoma and treated by Dr. Kim Margolin with a combination of immunotherapy and targeted therapies. Learn more about Mike’s incredible recovery and care.

As discussed above, both Dr. Kim Margolin and Dr. Przemyslaw Twardowski have multiple clinical trials, looking for optimized efficacy in new immunotherapy agents for melanoma and cutaneous skin cancers and genitourinary cancers such as kidney, bladder, prostate, and testicular cancer. With decades of practicing medicine, both experts under one roof are the future of care Dr. Donald L. Morton saw when he first started his research in the 1980s.

Be that as it may, clinical trials do not have to be a Hail Mary when the standard of care isn’t working. Sometimes, a clinical trial may offer the best first line of treatment in addition to the standard of care. Self-advocacy is a sentiment we often hear from our patients.

Learn the process of enrolling in a clinical trial here.

“There are times when a patient really wants to try a drug and they heard of it already…You don’t have an ordinary trial for them that would consist of multiple institutes participating…The FDA calls it ‘expanded access,’ or compassionate use protocols for individual patients…, a ‘right to try.’”

– Kim Margolin, MD

Access to Personalized Medicine and Immunotherapy

Addressing cost barriers and improving accessibility to immunotherapy treatments remains a critical goal.

Immunotherapy and Artificial Intelligence?

In a recent post by the NIH on June 3rd, 2024, they announced a new study in which scientists may predict immunotherapy response in cancer patients using Artificial Intelligence (AI). Dr. Margolin doesn’t see how this study pertains to melanoma. “Factors that may be useful in other tumors, particularly the tumor mutation burden and PD-L1 expression, don’t show enough variation in melanoma to act as discriminators for benefit from immunotherapy and we need deeper understanding of the mechanisms of action of each immunotherapy agent and of each type of melanoma before we can develop AI as a tool for predicting benefit,” disclosed Dr. Margolin.

Immunotherapy Research Funding

The need for continued research in immunotherapy and other immune response vaccines is imperative as Dr. Twardowski mentions, “There’s still so much we don’t know.” Advances in care approach, personalized medicine, and specialists in the field continue to make strides at Saint John’s Cancer Institute, along with their staff and administrators. Though, we still have the need for support to deepen our understanding into tumor responses, and the microenvironments.

If you can make a donation to our research please follow the link, and thank you on behalf of our researchers, staff, and clinicians.

Click here to make a donation.

Checkpoint Inhibitor Terminology:

PD-1 is a receptor protein found on the surface of specific immune cells, particularly T-cells. The discovery of PD-1 revolutionized cancer treatment by developing PD-1 pathway inhibitors, also known as checkpoint inhibitors. The first one was FDA-approved in 2014 (nivolumab) and 2015 (pembrolizumab), of which Saint John’s participated in those clinical trials under the previous medical director, Dr. O’Day.

PD-L1 is a protein expressed on the surface of various cells, including cancer cells, immune cells, and specific normal tissues. Its primary function is interacting with the PD-1 receptor on T cells and delivering inhibitory signals that suppress T cell activity. The discovery of PD-L1’s role in immune evasion by cancer cells led to the development of therapies targeting the PD-1/PD-L1 pathway, known as checkpoint inhibitors. Antibodies that block PD-L1 (such as atezolizumab, durvalumab, and avelumab) prevent its interaction with PD-1, thereby releasing the brakes on T cells and enhancing their ability to recognize and attack cancer cells.

About the Author

Eleanor Zeri