Cancer Vaccine Plus Interleukin-7 Boosts Immune Response to Cancer

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Cancer Vaccine Plus Interleukin-7 Boosts Immune Response to Cancer

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Scientists have discovered that combining interleukin-7 (IL-7) – a key component of the immune system – with a viral vaccine improves the ability of the immune system to attack tumors. A Canadian team at The Campbell Family Institute for Breast Cancer Research (CFIBCR) at Princess Margaret Hospital, Toronto say their discovery could be included in new clinical trials that use a patient’s own cells to destroy tumors.

The findings, published online today in Nature Medicine, demonstrate the tantalizing potential of immunotherapy in cancer treatment, says principal investigator Dr. Pamela Ohashi, co-director, CFIBCR.

In the lab study performed on animals. Dr. Ohashi says, the result was clear -- combining interleukin-7 (IL-7) with a viral vaccine boosted immunity to tumors.

“We are extremely excited because our research has revealed the unexpected ways IL-7 works to break down barriers that naturally block the immune response to tumors,” says Dr. Ohashi, a senior scientist in signaling biology who holds a Canada Research Chair in Autoimmunity and Tumor Immunity. She is also a Professor, University of Toronto, in the Department of Medical Biophysics and Immunology.

Dr. Tak Mak, co-author and CFIBCR director, says: "The promise of using the body’s own defenses to fight cancer is enormous. The day is coming when immunotherapy may help spare cancer patients the toxic side effects of traditional therapies and greatly improve their quality of life while treating the disease. This is why we are planning to expand our immunotherapy research program at PMH." Dr. Mak is also a Professor, University of Toronto, in the Department of Medical Biophysics and Immunology.

This research was also financially supported by grants and fellowships from the Canadian Institute for Health Research, the Ontario Institute for Cancer Research, the Terry Fox Foundation, the National Cancer Institute of Canada, the Boninchi Foundation (Geneva) and the Irvington Institute with the Cancer Research Institute (New York).

About The Campbell Family Institute for Breast Cancer Research
The Campbell Family Institute for Breast Cancer Research at Princess Margaret Hospital brings together an elite team of cancer researchers, scientists, clinicians and staff dedicated to the ultimate goal of conquering breast cancer by leveraging basic, translational and clinical research into dramatic breast cancer breakthroughs. www.campbellfamilyinstitute.com

About Princess Margaret Hospital
Princess Margaret Hospital is a member of University Health Network, which also includes Toronto General Hospital and Toronto Western Hospital. All three are research hospitals affiliated with the University of Toronto. www.uhn.on.ca

LINKS

Dr. Tak Mak's research bio at CFIBCR

Dr. Pamela  Ohashi's research bio at CFIBCR

 A clinical trial "Interleukin-7 and Vaccine Therapy in Treating Patients With Metastatic Melanoma" began in 2004 and has been completed. As yet no study results have been announced.  A trial of interleukin alone for patients with advanced cancer -- Interleukin-7 in Treating Patients With Refractory Solid Tumors -- is ongoing in Washington D.C. and in Texas (no longer recruiting). 

Today's publication in NATURE MEDICINE with editorial comment: "Interleukin-7 (IL-7) promotes immune responses and has been touted as a potential tool for improving immune targeting of tumors. Here Pellegrini et al. investigate the mechanisms by which IL-7 increases antitumor responses and the treatment strategies necessary to optimize its effects."

Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies

Marc Pellegrini, Thomas Calzascia, Alisha R Elford, Arda Shahinian, Amy E Lin, Dilan Dissanayake, Salim Dhanji, Linh T Nguyen, Matthew A Gronski, Michel Morre, Brigitte Assouline, Katharina Lahl, Tim Sparwasser, Pamela S Ohashi & Tak W Mak

Published online: 26 April 2009 |

Identifying key factors that enhance immune responses is crucial for manipulating immunity to tumors. We show that after a vaccine-induced immune response, adjuvant interleukin-7 (IL-7) improves antitumor responses and survival in an animal model. The improved immune response is associated with increased IL-6 production and augmented T helper type 17 cell differentiation. Furthermore, IL-7 modulates the expression of two ubiquitin ligases: Casitas B-lineage lymphoma b (Cbl-b), a negative regulator of T cell activation, is repressed, and SMAD-specific E3 ubiquitin protein ligase-2 (Smurf2) is enhanced, which antagonizes transforming growth factor-beta signaling. Notably, we show that although short term IL-7 therapy potently enhances vaccine-mediated immunity, in the absence of vaccination it is inefficient in promoting antitumor immune responses, despite inducing homeostatic proliferation of T cells. The ability of adjuvant IL-7 to antagonize inhibitory networks at the cellular and molecular level has major implications for immunotherapy in the treatment of tumors.

MORE ON INTERLEUKIN-7 

IL-7 boosting T-cells outside the thymus
IL-7 stimulating T-cells outside of the thymus
Click for large version. Diagram from Interleukin-7: from bench to clinic,
Terry J. Fry and Crystal L. Mackal,
Blood, 1 June 2002, Vol. 99

T lymphocytes (T cells) are white blood cells that are active in the immune system. They're called T cells or T-lymphocytes because they pass through the Thymus and are modified there before coming to maturity. The thymus is an organ located in the upper front chest behind the breast bone (sternum).  The thymus gland is part of the lymphatic immune system  T cells are differentiated, develop and mature in the thymus before entering the circulation.

In humans, the thymus reaches full size at puberty and gradually shrinks throughout the adult years. In people of age 50 it is less than a quarter of it peak size. Even in younger people thymic function can be reduced by illness and it can be reduced in people of any age by certain therapies such as chemotherapy for cancer. 

How the immunologic function of the thymus was discovered

 The function of the thymus was discovered by Jacques Miller in 1961. He was the first to show that the thymus is essential for the normal development of the immune system.Thirty years earlier, Edith Boyd showed that the thymus reaches full size at sexual maturity and shrinks as people age. The following New York Times article from 1983 shows how Miller's discover stirred up interest in the thymus and longevity:

MYSTERIOUS THYMUS GLAND MAY HOLD THE KEY TO AGING

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