Retired self-proteins as vaccine targets for primary immunoprevention of adult-onset cancers

Abstract

We propose that optimized control of adult-onset cancers requires the incorporation of a defense-based strategy in the form of preemptive immunity induced in healthy cancer-free subjects prior to the appearance of tumors. However, development of such prophylactic immunity has traditionally targeted etiopathogenic agents. We propose that in the absence of available cancer-inducing pathogens, safe and effective protection against the emergence of tumors may be achieved by inducing targeted immunity against tissue-specific self-proteins that are ‘retired’ from expression at immunogenic levels in normal tissues due to the normal aging process, but are expressed in emerging tumors. Thus, ‘retired’ self-proteins may substitute for unavailable pathogens as targets for developing prophylactic immunity against tumors we confront with age like breast, ovarian and prostate cancer. Our current efforts involve testing this primary ‘immunoprevention’ strategy in clinical trials focused on prevention of the more aggressive and lethal forms of breast cancer.

Keywords::

• α-lactalbumin
• autoimmunity
• breast cancer
• cancer vaccines
• immunoprevention
• T cells
• triple-negative breast cancer

Acknowledgements

The author wishes to recognize and express his sincere gratitude for the support and encouragement received from a variety of people and organizations that have been instrumental in making this work possible including Mort and Iris November from November Philanthropy, Leigh Anne Best and Laura Franks from Brakes for Breasts, Toni Turchi from the Toni Turchi Foundation, Dr Kathleen Ruddy from the Breast Health and Healing Foundation, Dr Marjorie Moyar and Susan Larson from the Coalition of Women Who Care About Breast Cancer, Judy Fitzgerald from the Sisters for Prevention, Tobey Young from the Previvors and Survivors, Loucinda Sullivan and Elyn Jacobs from the Champions of the Pink Vaccine, Josh and Danielle Berns from The Race at Legacy Village, Thea Pelecanos from The National Greek Orthodox Ladies Philoptochos Society and the Daughters of Penelope Icarus Chapter 321, Brandon Scott Perry from Can't Stop Won't Stop, and Deborah Marotta from Walk With A Doc.

Financial & competing interests disclosure

VK Tuohy is the inventor of vaccines based on the retired self-protein strategy, and these vaccines have been licensed to Shield Biotech, Inc., a privately owned company. This work was supported by a grant from Shield Biotech, Inc., Cleveland, OH. VK Tuohy is the Chief Science Officer of Shield Biotech and may in the future receive commercialization revenues for this technology. The author acknowledges that there is a potential conflict of interest related to his relationship with Shield Biotech and asserts that to the best of his ability he has taken all measures in this report to avoid any inappropriate bias associated with the commercial goals of the company. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Primary immunoprevention of cancer refers to preventing the occurrence of cancer in otherwise healthy, cancer-free subjects.

• Secondary immunoprevention of cancer refers ro preventing the recurrence of cancer in patients already diagnosed with disease and as such is a treatment.

• The treatment paradigm predominates in the current control of adult-onset cancers.

• There is a prominent deficiency in our current healthcare devoid of primary immunoprevention against diseases we commonly encounter with age like breast, ovarian and prostate cancer.

• Safe and effective protection against the emergence of tumors may be achieved by inducing targeted immunity against tissue-specific proteins that are ‘retired’ from expression at immunogenic levels in normal tissues as a result of the normal aging process but are expressed in emerging tumors.

• ‘Retired’ self-proteins may substitute for unavailable pathogens as targets for developing primary immunoprevention against cancers that commonly occur with age.

• Two paradigm changing viewpoints are proposed: breast cancer may be substantially controlled by primary immunoprevention and such prophylactic immunity may be achieved without targeting pathogens.

• Numerous self-proteins have been proposed as targets for vaccine-induced prevention of breast cancer but many are poorly immunogenic and/or expressed in numerous normal tissues, thereby predisposing to either unresponsiveness or induction of autoimmune complications.

• α-Lactalbumin protein may be targeted for vaccine-induced primary immunoprevention of breast cancer because it is normally expressed at immunogenic levels only in human lactating breast tissue and is overexpressed in the majority of triple-negative breast cancer, the most aggressive and lethal form of breast cancer.

• Immunoprevention of breast cancer will not likely be available for general application until at least 2024.

• Proteins that are retired from expression with age in the normal human ovary or prostate and are expressed in tumors derived from these organs may also serve as targets for primary immunoprevention of these adult-onset cancers.

Notes