Immunotherapy Plus Cryotherapy: Potential Augmented Abscopal Effect for Advanced Cancers

[D.ap]

Abstract
Since the 1920s the gold standard for treating cancer has been surgery, which is typically preceded or followed with chemotherapy and/or radiation, a process that perhaps contributes to the destruction of a patient’s immune defense system. Cryosurgery ablation of a solid tumor is mechanistically similar to a vaccination where hundreds of unique antigens from a heterogeneous population of tumor cells derived from the invading cancer are released. However, releasing tumor-derived self-antigens into circulation may not be sufficient enough to overcome the checkpoint escape mechanisms some cancers have evolved to avoid immune responses. The potentiated immune response caused by blocking tumor checkpoints designed to prevent programmed cell death may be the optimal treatment method for the immune system to recognize these new circulating cryoablated self-antigens. Preclinical and clinical evidence exists for the complementary roles for Cytotoxic T-lymphocyte-associated protein (CTLA-4) and PD-1 antagonists in regulating adaptive immunity, demonstrating that combination immunotherapy followed by cryosurgery provides a more targeted immune response to distant lesions, a phenomenon known as the abscopal effect. We propose that when the host’s immune system has been “primed” with combined anti-CTLA-4 and anti-PD-1 adjuvants prior to cryosurgery, the preserved cryoablated tumor antigens will be presented and processed by the host’s immune system resulting in a robust cytotoxic CD8+ T-cell response. Based on recent investigations and well-described biochemical mechanisms presented herein, a polyvalent autoinoculation of many tumor-specific antigens, derived from a heterogeneous population of tumor cancer cells, would present to an unhindered yet pre-sensitized immune system yielding a superior advantage in locating, recognizing, and destroying tumor cells throughout the body

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882833/

[D.ap]

Introduction
In the era of molecular medicine, the oncology field still faces many extreme challenges extending survival rates to all stage III and IV cancers with many cancers remaining particularly arduous to treat. Five-year survival rates for lung, liver, and esophageal cancers have hovered around only 15% for decades (1). Other diseases, such as mesothelioma, pancreatic carcinoma, and glioblastomas, have only single digit 5-year survival rates (1). All cancers with distant metastases have less than a 10% 5-year survival. For many of these difficult challenges, new approaches to extend survival are under constant clinical investigation. Herein, we propose a novel approach combining two dependable oncology-based treatment platforms to potentially cause a synergistic immune response to target loco-regional and distant cancer metastases efficiently.

[D.ap]

From the first opening paragraph

“Based on recent investigations and well-described biochemical mechanisms presented herein, a polyvalent autoinoculation of many tumor-specific antigens, derived from a heterogeneous population of tumor cancer cells, would present to an unhindered yet pre-sensitized immune system yielding a superior advantage in locating, recognizing, and destroying tumor cells throughout the body”
The 2 different kinds of antigens : )

“Non-Self Antigens, Self-Antigens & Allergens”

https://study.com/academy/lesson/non-se ... rgens.html

Tumor specific antigen

https://www.cancer.gov/publications/dic ... ic-antigen

[D.ap]

From introduction and focus to the article -


“Herein, we propose a novel approach combining two dependable oncology-based treatment platforms to potentially cause a synergistic immune response to target loco-regional and distant cancer metastases efficiently.”

[D.ap]

syn·er·gis·tic
ˌsinərˈjistik/Submit
adjective
adjective: synergistic
relating to the interaction or cooperation of two or more organizations, substances, or other agents to produce a combined effect greater than the sum of their separate effects.
"the synergistic interaction of mind and body"