James P. Allison, PhD, chair, Immunology, executive director, Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, recipient, 2018 Nobel Prize in Physiology or Medicine, discusses his experience with the urgency of drug development in oncology. 

There was a lot of urgency in the early days of developing ipilimumab (Yervoy) when the antibody was made, Allison says. In the clinic, Allison was trying to hurry the development of ipilimumab along because his brother had metastatic castration-resistant prostate cancer. He was hoping that the drug may be available for use in his brother’s treatment; however, therapeutic development could only move so fast, Allison adds.

Nevertheless, the development of ipilimumab made Allison appreciate efficiency in conducting science-based work, he continues. Although speed is important during drug development, getting the science right is just as important, Allison concludes.

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James P. Allison, PhD, discusses his experience with the urgency of drug development in oncology. 

Dr. Allison on the Urgency of Drug Development in Oncology

James P. Allison, PhD, chair, Immunology, executive director, Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, and a recipient of the 2018 Nobel Prize in Physiology or Medicine, discusses the impact of immunotherapy on patients with cancer. 

Immunotherapy is a pillar of cancer treatment and deserves to be recognized as such, Allison says. Moreover, immunotherapy has the potential to be curative as new molecules are developed and investigated as both monotherapies, and in combination with conventional therapies, Allison continues. The magnitude of immuno-oncology is promising, and new developments in the space have the potential to cure many more patients with cancer, Allison concludes. 

James P. Allison, PhD, discusses the impact of immunotherapy on patients with cancer. 

Dr. Allison on the Impact of Immunotherapy in Cancer 

James P. Allison, PhD, chair, Immunology, executive director, Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, and a recipient of the 2018 Nobel Prize in Physiology or Medicine, discusses the development of ipilimumab (Yervoy).

When developing ipilimumab, a monoclonal antibody, bias against immunotherapy presented the biggest challenge at the time, according to Allison. Allison focused his research on mechanisms and the regulation of T-cell responses and tried to apply this work to the treatment of patients with cancer. During his research, he found that blocking checkpoints could unleash the immune system’s T cells. 

Allison anticipated doubts about this strategy, and he completed research in mouse models with various strains and tumors to ensure ipilimumab would work as monotherapy, radical chemotherapy, radiation, or vaccine.

James P. Allison, PhD, discusses the development of ipilimumab.

Dr. Allison on the Development of Ipilimumab for Cancer Treatment 

James P. Allison, PhD, chair, Immunology, executive director, Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, and a recipient of the 2018 Nobel Prize in Physiology or Medicine, discusses his early career at The University of Texas MD Anderson Cancer Center.

Allison completed his first faculty appointment at The University of Texas MD Anderson Cancer Center. He had an early interest in immunology and T cells, which first began to be recognized in the late 1960s, according to Allison. As a biochemist, Allison decided that he wanted to focus his research efforts on T cells were, but he did not receive the chance to until his faculty appointment at MD Anderson, Allison says.

Allison finished his postdoctoral research at an immunology lab, where he did protein purification. When he arrived at MD Anderson, he was able to indulge his curiosity and work out the structure of the T-cell antigen receptor, which propelled him into his subsequent research, Allison concludes.

James P. Allison, PhD, discusses his early career at The University of Texas MD Anderson Cancer Center.

Dr. Allison on His Early Career at The University of Texas MD Anderson Cancer Center 

James P. Allison, PhD, chair, Immunology, executive director, Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, and a recipient of the 2018 Nobel Prize in Physiology or Medicine, discusses his research on reverse translation in cancer. 

Reverse translation, which is largely clinical trial–based, involves collecting specimens from patients on trials and observing the mechanisms for insight into new combination therapies, according to Allison. Previous research has demonstrated the components of a good signal, including T cells, myeloid cells, and fibroblasts, and this research aims to dissect that further, Allison adds. 

Once the critical observations have been made with the samples in the laboratory, mouse experiments are used to test hypotheses before the process is repeated with an iteration of change, Allison continues. Progress has been made with this method, particularly in genitourinary cancers, Allison says. This strategy is also being examined in pancreatic cancer and glioblastoma multiforme with the goal of making therapies work better, Allison concludes. 

James P. Allison, PhD, discusses his research on reverse translation in cancer. 

Dr. Allison on Reverse Translation in Cancer Research  

James P. Allison, PhD, chair of Immunology and executive director of the Immunotherapy Platform at The University of Texas MD Anderson Cancer Center, and a recipient of the 2018 Nobel Prize in Physiology or Medicine, discusses the future of immunotherapy in the treatment of patients with cancer.

Allison says that when he began his work in immunology, the mechanism of T cells was largely unknown. He says that the current understanding is still only scratching the surface—it is a dynamic process. If immunotherapy is going to be used in the treatment of patients with cancer, the mechanisms of T cells need to be understood. This is particularly pertinent to the conversation about combination immunotherapy. Immunotherapy in combination with genomic or targeted kinase inhibitors can be powerful, but Allison warns that the effect on the immune system is not yet known.

Immunotherapy has become the fourth pillar of cancer care, joining surgery, radiation, and chemotherapy. These 3 modalities have been traditionally separated into siloes, Allison explains, but immunotherapy is unique—it can work well with all 3 modalities. The goal now is figuring out a universal way of combining these modalities and hope for synergy, he concludes.

Dr. Allison Discusses the Future of Immunotherapy in Cancer Care

James Allison, PhD, chair of Immunology at the University of Texas MD Anderson Cancer Center, discusses promising data regarding the use of immunotherapies in melanoma. Allison is particularly excited about a trial, presented at the Society of Melanoma Research Congress, which looked at the combination of PD-L1 inhibitors with a 

In one setting, there was a nearly 100% response rate, he says. MEK inhibitors, which were previously thought to be unlikley to produce T-cell responses because T cells need that pathway, also have shown promise says Allison.

It has been determined that they are not as destructive to immune responses as previously thought. It may be possible to work out proper dosing levels and really take advantage of MEK inhibitors in treating melanoma effectively, he says.

James Allison, chair of Immunology at the University of Texas MD Anderson Cancer Center, discusses promising data regarding the use of immunotherapies in melanoma. Allison is particularly excited about a trial, presented at the Society of Melanoma Research Congress, which looked at the combination of PD-L1 inhibitors with a BRAF-targeted agent.

James Allison on Exciting Immunotherapy Advancements in Melanoma

James P. Allison, PhD, director, immunotherapy platform, The University of Texas MD Anderson Cancer Center, Giant of Cancer Care, discusses the potentiation of immune checkpoint blockade cancer immunotherapy with oncolytic viruses.

The checkpoint blockage works by enhancing priming of T cells when tumor cells are being killed, which causes an inflammatory response, Allison says. Oncolytic viruses either cause an innate immune response or kill the tumor cells while excreting antigens that lead to more priming of T cells.

Allison says research has shown that when a virus accomplishes both of these things, the priming of the T cells can be potentiated by immune checkpoint blockade.

Researchers are working on a second generation of oncoloytic viruses that cause co-stimulation of T cells, which will increase the efficacy, Allison says.

James P. Allison, PhD, director, immunotherapy platform, The University of Texas MD Anderson Cancer Center, Giant of Cancer Care, discusses the potentiation of immune checkpoint blockade cancer immunotherapy with oncolytic virus.

James P. Allison, PhD

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