Long-term memory T cells as preventive anticancer immunity elicited by TuA-derived heteroclitic peptides

Abstract

The host’s immune system may be primed against antigens during the lifetime (e.g. microorganisms antigens—MoAs), and swiftly recalled upon growth of a tumor expressing antigens similar in sequence and structure. C57BL/6 mice were immunized in a preventive setting with tumor antigens (TuAs) or corresponding heteroclitic peptides specific for TC-1 and B16 cell lines. Immediately or 2-months after the end of the vaccination protocol, animals were implanted with cell lines. The specific anti-vaccine immune response as well as tumor growth were regularly evaluated for 2 months post-implantation. The preventive vaccination with TuA or their heteroclitic peptides (hPep) was able to delay (B16) or completely suppress (TC-1) tumor growth when cancer cells were implanted immediately after the end of the vaccination. More importantly, TC-1 tumor growth was significantly delayed, and suppressed in 6/8 animals, also when cells were implanted 2-months after the end of the vaccination. The vaccine-specific T cell response provided a strong immune correlate to the pattern of tumor growth. A preventive immunization with heteroclitic peptides resembling a TuA is able to strongly delay or even suppress tumor growth in a mouse model. More importantly, the same effect is observed also when tumor cells are implanted 2 months after the end of vaccination, which corresponds to 8 – 10 years in human life. The observed potent tumor control indicates that a memory T cell immunity elicited during the lifetime by a antigens similar to a TuA, i.e. viral antigens, may ultimately represent a great advantage for cancer patients and may lead to a novel preventive anti-cancer vaccine strategy.

Peptides as Therapeutic Agents: Challenges and Opportunities in the Green Transition Era

“…These results indicated that tumor growth can be controlled by an established T cell memory specific for antigens structurally related with a TuA. This response was achieved by the authors exploiting synthetic hPep specifically designed from TuA sequences [74].…”

“…Many ACPs are in fact endowed with immunomodulatory properties that can be harnessed to effectively counteract tumor growth [48,53]. In 2021, Mauriello et al probed the viability of immunizing C57BL/6 mice by administering tumor antigens (TuAs) or the corresponding heteroclitic peptides (hPep), i.e., variants of native peptides designed to stimulate stronger T cell responses [74]. Upon completion of the vaccination protocol, animals were implanted with tumor cell lines, and the specific anti-vaccine immune response, along with tumor growth, were evaluated.…”

An Overview of the Immune Modulatory Properties of Long Non-Coding RNAs and Their Potential Use as Therapeutic Targets in Cancer

“…The adaptive immune system has memory cells that "remember" previous encounters with antigens, enabling it to respond more effectively upon re-exposure. Some cancer immunotherapies aim to establish immune memory to ensure long-term control and prevention of tumor recurrence [82].…”