Over the past two decades, immunotherapies have fundamentally reshaped cancer care. By harnessing the body鈥檚 immune system to recognize and destroy cancer cells, these treatments have delivered dramatic gains for patients with blood-based cancers 鈥 sometimes even making cures possible. But progress has not been uniform.
, the Robert E. and Emily H. King Professor of Cancer Research at RUSH MD Anderson Cancer Center, has devoted his career to researching and treating multiple myeloma. He has witnessed both the promise and limits of immunotherapy.
鈥淚mmunotherapy is how we treat most myeloma today,鈥 he said. 鈥淚t鈥檚 a very good example to showcase the advances of immunotherapy, but also where more progress is needed.鈥
When immune cells are engineered to attack cancer, whether in blood-based diseases or solid tumors, they are trained to recognize proteins expressed on the surface of tumor cells. But they struggle to penetrate and reach the heart of a tumor to clear the cancer completely.
With this knowledge, RUSH MD Anderson providers and scientists, including Dr. Asimakopoulos, are leading some of the most promising 鈥 and at times creative 鈥 investigations that will define the next frontier of cancer research and care.
Overcoming barriers: Advancing studies with potential to transform cancer care
Over the last decade, Dr. Asimakopoulos鈥 lab has studied how tumor cells keep immune cells out. Their findings have informed several immunotherapies, including a novel CAR T-cell concept that is now advancing to a preclinical mouse model study 鈥 a promising first step toward a human clinical trial.
Like other immunotherapies, CAR T has transformed care for many blood-based cancers, especially lymphoma and leukemia, but it is not routinely curative for myeloma. Dr. Asimakopoulos鈥 team is reengineering CAR T-cells based on their new understanding of tumor鈥慻enerated barriers.
鈥淥ur hope is that by overcoming these barriers, we will be able to not just kill more tumor cells but eradicate those myeloma lesions and get a step closer to a cure,鈥 Dr. Asimakopoulos said.
The preclinical mouse model will allow his lab to test its concept. If researchers can validate and replicate their findings in this model, they will have the evidence they need to launch early-phase clinical trials.
Advancing this kind of research requires more than scientific insight. It depends on infrastructure that can support high鈥憆isk, early鈥憇tage innovation. At RUSH MD Anderson, philanthropic investments have enabled Dr. Asimakopoulos to grow his research team, build out dedicated space within the Cell Therapy Center, and access resources and equipment to support the transition from lab research to clinical trials 鈥 and, eventually, cell manufacturing.
鈥淲e鈥檙e very happy to have the support to do this work here,鈥 he said. 鈥淚t鈥檚 a great new environment for me and my team.鈥
Dr. Asimakopoulos is not the only RUSH MD Anderson clinician-scientist moving immunotherapy research into a mouse model. Others are applying their concepts to solid tumors, which have fewer cellular-based therapeutic options.
Widening the scope: Applying immunotherapy to solid tumors
, a RUSH MD Anderson medical oncologist, has been fascinated by immunotherapies since their earliest days. Their promise attracted her to oncology. Seeing the limited benefits of some cancer therapies drove her to explore high-risk, high-reward research to reduce suffering.
鈥淥ncology is truly a rewarding field,鈥 she said. 鈥淎nd I want to see more of my patients leading longer lives. In my mind, Rush is a perfect place for conceiving and developing innovative cancer therapies.鈥
Recently, Dr. Usha and her team of basic science researchers have been investigating how fibroblasts, or connective tissue cells, shape the tumor microenvironment and affect the growth of solid tumors, particularly in breast and ovarian cancers. In a surprising turn, experiments using chicken embryonic fibroblasts showed the opposite of what researchers typically see: Instead of promoting tumor growth, the fibroblasts inhibited the growth of breast and ovarian cancer cell lines.
To test the concept in an animal model, Dr. Usha needed a partner. She found a nearly perfect match in , assistant professor in the Department of Internal Medicine, who has been harnessing immunologic approaches to find new treatments for triple-negative breast cancer.
鈥淚 thought Dr. Marzo would be the perfect collaborator,鈥 Dr. Usha explained. 鈥淢ost mouse models in her lab have a normal immune system. Researchers inject the mice with a triple-negative breast cancer cell line, wait for it to grow and then apply the treatment directly into the tumor.鈥
Over the last five years, Dr. Marzo鈥檚 laboratory has pioneered an innovative approach to cancer treatment by directly injecting FDA-approved vaccines into tumors using well-established mouse models. Their experiments have shown great promise in reducing and even eliminating tumors in breast cancer models.
鈥淭he vaccines are working in a way we didn鈥檛 expect,鈥 Dr. Marzo explained. 鈥淚mmune responses that are usually not considered helpful against cancer are, in this case, being redirected to help the body fight tumors."
Just as Dr. Usha was looking for a laboratory collaborator, Dr. Marzo was also searching for clinical partners to advance her work. This alignment has led to a growing collaboration with Dr. Usha and other clinicians at RUSH MD Anderson who are now working with Dr. Marzo to develop a preclinical trial across multiple cancer types, including head and neck, breast, lung and pancreatic.
鈥淲e would not be here without philanthropic support,鈥 Dr. Marzo said. 鈥淚n particular, support from Bears Care and Swim Across America enabled us to generate the critical preliminary data that ultimately led to funding from the U.S. Department of Defense.鈥
Harnessing hope: What the future holds
The FDA approved the first targeted therapy for cancer in 2011. The landmark drug, known as ipilimumab, revolutionized cancer care for metastatic melanoma and meaningfully increased life expectancy. Ipilimumab ushered in the era of immunotherapy. In less than a generation, more than 150 immunotherapies 鈥 including immune checkpoint inhibitors, cell therapies and antibodies 鈥 have received FDA approval. Some have had curative effects.
The preclinical experiments taking place at RUSH MD Anderson offer hope that similar outcomes for myeloma and solid tumors are within reach.
鈥淚t鈥檚 hard for us in the multiple myeloma field to give patients this diagnosis,鈥 Dr. Asimakopoulos said. 鈥淓ven after 20 years, it鈥檚 just as hard now as it was on the first day.鈥
Immunotherapy has the potential to generate long-lasting immunity that can prevent relapses and keep cancers like multiple myeloma at bay for a long time.
鈥淢y hope is that, in another 10 years, we have unlocked these mysteries and have more options for people with myeloma that could even be curative,鈥 he said.
Dr. Usha maintains the same positive outlook.
鈥淚鈥檝e thought a lot about conventional therapies,鈥 she said. 鈥淏ut we need to look at truly novel ones. Then, maybe someday, we鈥檒l stop signing death certificates. Nothing moves forward if we don鈥檛 have hope.鈥
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All philanthropic gifts benefit initiatives of RUSH MD Anderson Cancer Center in the greater Chicago area and Northwest Indiana and do not fund research or programs at The University of Texas MD Anderson Cancer Center in Houston.
