A 3-D Tumor Microenvironment for Personalized Immunotherapy

A new platform enables screening a wide range of combination anticancer therapeutics in a matter of days, which may translate to personalized therapeutic regimens for patients in less time.

Roni Dengler, PhD
Sep 10, 2021

Immunotherapies in pancreatic and breast cancers—two prominent and lethal cancer types—are not a home run on their own. These therapies often benefit from working in combination with other treatments, such as antibodies or drugs. 

Jonathan Dordick, a chemical and biological engineer at Rensselaer Polytechnic Institute, and an international team of collaborators, developed a platform that can help identify which therapy combinations will most benefit a patient. 

Researchers can now test 3-D tumor spheroids, immune cells, antibodies, and chemotherapies in a single screening platform.
Gopal et al.

The researchers developed a chip that encourages immune cells and cancer cells to grow together in three-dimensions, recapitulating the tumor microenvironment. The platform enables rapid screening of anticancer therapies for developing personalized immunotherapies.

“This kind of high-throughput and easy-to-use cell culture and analysis platform is highly desired for characterizing complex immune responses and elucidating their underlying mechanisms in clinical settings,” Moo-Yeal Lee, a biomedical engineer at the University of North Texas, who was not involved in the research, wrote in an email. 

Solid tumors are an impediment to immunotherapies. The tumor microenvironment, replete with supportive tissue and procancer immune cells, prevents anticancer immune cells, such as effector T cells, from multiplying. Combining immunotherapies with other treatment modalities, such as antibodies or small molecule chemotherapies, however, shows increasing promise in the clinic. Unfortunately, screening multiple therapeutic combinations for cytotoxic efficacy in a high-throughput manner is currently not feasible. 

In a study published in Communications Biology, Dordick and his team printed 3-D breast and pancreatic tumor spheroids in hydrogel on a pillar plate, where cells grow on raised pedestals rather than in wells. They then coupled the pillar plate to a well plate containing natural killer immune cells, antibody therapies, and chemotherapies. 

“This effectively functions to better mimic what happens in a patient,” Dordick said.

The platform models the tumor microenvironment better than 2-D or 3-D cell culture. When the researchers cultured natural killer immune cells and pancreatic cancer or breast cancer cells in combination with antibody therapies, the combo boosted cytotoxicity in the cancer cells. 

“It was quite intriguing that cytotoxicity of cancer cells by immune cells was enhanced by placing the sandwiched plates upside down,” Lee said. “This may indicate that cell death is induced mainly due to direct contact between cancer cells and immune cells.”

Lee also noted that the researchers conducted the study in commercial cell lines. “It would be highly impactful if tumor organoids or immune cells derived from patients are used in the study,” Lee said.

Dordick and his team are working on that. They designed the platform to facilitate using a patient’s biopsy sample, screening a range of drug combinations, and determining within a matter of days which therapeutic regimen works best for the patient.

“We’ve shown that the anticancer activity of a combination of natural killer cells, the immune cells together with antibody, [and] small molecule chemotherapeutic can be quite powerful, and that under various conditions can work very well against solid tumor cell types,” Dordick said. “We feel that this could be a significant opportunity to provide the best therapeutic pathways for cancer patients and to do it very quickly.” 

Reference

S. Gopal et al., “3D tumor spheroid microarray for high-throughput, high-content natural killer cell-mediated cytotoxicity,” Commun Biol, 4(1):1-14, 2021.