Oncolytic immunotherapy: multiple mechanisms of oncolytic peptides to confer anticancer immunity

Abstract

Oncolytic peptides are highly effective on remodeling the tumor microenvironment and potentiating the anticancer immunity through multiple mechanisms, particularly by inducing immunogenic cell death. Intriguingly, a recent study demonstrates that LTX-315, one of the most promising and extensively studied oncolytic peptides, inhibits PD-L1 expression via ATP11B, thus enhancing the effectiveness of cancer immunotherapy by targeting the PD-1/PD-L1 axis. Therefore, this commentary discusses the broad effects and perspectives of oncolytic peptides on anticancer immunity, further highlighting the potential issues and directions of oncolytic peptides in cancer immunotherapy.

Engineering nanomedicines for immunogenic eradication of cancer cells: Recent trends and synergistic approaches

“…Oncolytic peptides demonstrate a high degree of efficacy in altering the TME and enhancing anticancer immune responses. This is achieved through various mechanisms, notably by triggering ICD 80 . The amphipathic cationic oncolytic peptide LTX-315 was found to promote the release of DAMPs including HMGB1 and chemokine CXCL10 via a different mechanism than chemotherapeutics.…”

“…For example, drugs act by inducing quiescence of the immunosuppressive cancer associated fibroblasts, drugs that suppress the activity or infiltration of the immunosuppressive Tregs or MDSCs can be good candidates for combination with ICD inducers via nanomedicine platforms to boost their immunogenic response. Comparison of different ICD inducer strategies are summarized in Table 3 60 , 62 , 66 , 67 , 74 , 80 , 172 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 .…”

Biomaterials That Induce Immunogenic Cell Death

“…However, the mechanism remains unclear. [61,62] Zhou and co-authors reported a cationic amphiphilic peptide, LTX-315, permeating the inner mitochondrial membrane and induced necrosis, leading to immune cell infiltration. [63] Based on assays of ICD hallmarks (CRT, ATP, HMGB1, and type-1 interferon response), LTX-315 induces ICD in a caspase-independent manner.…”

Three Rounds of Stability-Guided Optimization and Systematical Evaluation of Oncolytic Peptide LTX-315

“…Recently, oncolytic peptides possessing synergistic oncolytic-immunotherapy effect have emerged as one of the main subsets of anticancer peptides and potential anticancer agents. ,, Oncolytic peptides are a class of surface-acting membrane-disrupting peptides, such as CAMP-derived peptide (LL-37), bovine lactotransferrin (LTF)-derived peptides, animal venoms and toxins-derived peptides, as well as the synthetic oncolytic peptides represented by “peptide 11″, , SVS-1 and (KAAKKAA) 3 . , Oncolytic peptides could disrupt the integrity of cancer cell membrane, penetrate cells, and destroy the intracellular membrane, the combined actions of which could induce the rapid death of cancer cells. , …”