On SAGE Insight: Curing cancer: How has immunotherapy transformed treatment in your particular specialty?

 

Professor Pio Conti, of University of Chieti-Pescara, is Editor of the European Journal of Inflammation and the International Journal of Immunopathology and Pharmacology

“In 1985, Steven A. Rosenberg and colleagues at the National Institutes of Health published an interesting article in the New England Journal of Medicine on the early results of LAK (lymphokine-activated killer) therapy, consisting of the systemic administration of autologous lymphocytes activated with rIL-2 to patients with advanced cancer. The article aroused great interest in public opinion and scientific researchers, but the serious side effects of this therapy led to the abandonment of this idea.

After more than 30 years, immunotherapy has been resumed and has evolved on the study of chimeric antigen receptor (CAR) T cells, which is a genetically engineered immune cell therapy for acute lymphoblastic leukemia.

CARs are made from patient T cells extracted from the blood and genetically modified to generate CARs. These cells are better cancer fighters. In fact, when they are infused back to the patient the CAR T cell receptors recognize unique proteins on the cancer cells and destroy them.

This is a promising, powerful and revolutionary approach to cancer therapy that uses the infusion of the patient’s own immune cells, genetically modified to recognize and kill cancer cells.

However, this therapy produces cytokine-mediated inflammation that must be absolutely inhibited. We propose the therapeutic use of IL-37, a new anti-inflammatory cytokine capable of down-regulating  IL-1 inflammatory cytokine family members, and stimulating IL-10.”

Sara Hurvitz, MD, of University of California, Los Angeles, is an Associate Editor of Therapeutic Advances in Medical Oncology

“Evidence of the benefits of immunotherapy for the treatment of several types of cancer has led to justifiable excitement. However, results from studies evaluating immunotherapy for the management of breast cancer have been somewhat disappointing to date.

While durable responses have been reported, tumor shrinkage is rare, especially in patients who have been previously treated for metastatic disease. Moreover, no biomarker or tumor subtype has been identified to date that reliably predicts those patients most likely to respond.

It is my view that outside of a clinical trial (and outside of the rare patient who has been identified to have a microsatellite instability (MSI)-high or mismatch repair (MMR)-deficient tumor), immunotherapy has no role at this time for the routine management of breast cancer.

That said, I strongly encourage, and am eager to be a part of, the development of rationally designed clinical trials evaluating novel immunotherapies. I’m especially interested in studies that evaluate these therapies in patients who have a relatively intact immune system (e.g. patients who have not received chemotherapy yet for their disease), as the chance of eliciting an anti-tumor immune response is higher in a person whose immune system has not been battered by cytotoxic therapy.

I’m also quite interested in studies that involve serial tumor biopsies (pre- and post-treatment) as these studies enable us to evaluate changes in the tumor and microenvironment that may be predictive of response or resistance to these approaches.”

Antonio Rossi, MD, of the Scientific Institute for Research and Health Care (IRCCS) Casa Sollievo della Sofferenza, is an Associate Editor of Therapeutic Advances in Medical Oncology

“Since 2015, a milestone year for the treatment of lung cancer due to the first worldwide approval of immunotherapy drug nivolumab for lung cancer, there has been ongoing excitement surrounding the role of immunotherapeutic drugs.

Immunotherapies stimulate a patient’s immune system to recognize and destroy cancer cells more effectively. Three such drugs – nivolumab, pembrolizumab and atezolizumab – are now approved for the treatment of all types of advanced non-small cell lung cancer (NSCLC), and the recent availability of these drugs has greatly changed patient treatment, improving both length and quality of life.

While nivolumab and atezolizumab are approved after chemotherapy regardless of the expression levels of a protein called PD-L1 (found on tumor cells), pembrolizumab is used following chemotherapy in adults whose tumors show some degree of PD-L1 expression. Pembrolizumab is also approved for the first-line treatment (i.e., alongside or instead of chemotherapy) of patients with PD-L1 expression in over 50% of cells, as there is a greater chance of pembrolizumab working better than chemotherapy in these patients; however, only about 30% of patients have very high levels of PD-L1 expression. Unfortunately, not everyone benefits from immunotherapy, and researchers are investigating the mechanisms of these treatments and factors useful in identifying the patients who may benefit the most from immunotherapy. There is still a long way to go, but there is certainly great potential for immunotherapy to further revolutionize the treatment of lung cancer.”

     
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