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Oncolytic peptides DTT-205 and DTT-304 induce complete regression and protective immune response in experimental
Karianne Giller Fleten1,2, J Johannes Eksteen3, Brynjar Mauseth4
1Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0379, Oslo, Norway.
Abstract:
Oncolytic peptides represent a novel, promising cancer treatment strategy with activity in a broad spectrum of cancer entities, including colorectal cancer (CRC). Cancer cells are killed by immunogenic cell death, causing long-lasting anticancer immune responses, a feature of particular interest in non-immunogenic CRC. Oncolytic peptides DTT-205 and DTT-304 were administered by intratumoral injection in subcutaneous tumors established from murine CRC cell lines CT26 and MC38, and complete regression was obtained in the majority of animals. When cured animals were rechallenged by splenic injection of tumor cells, 1/23 animals developed liver metastases, compared to 19/22 naïve animals. Treatment with both peptides was well tolerated, but monitoring post-injection hemodynamic parameters in rats, less extensive changes were observed with DTT-205 than DTT-304, favoring DTT-205 for future drug development. DTT-205 was subsequently shown to have strong in vitro activity in a panel of 33 cancer cell lines. In conclusion, both peptides exerted a strong inhibitory effect in two immunocompetent CRC models and induced a systemic effect preventing development of liver metastases upon splenic rechallenge. If a similar effect could be obtained in humans, these drugs would be of particular interest for combinatory treatment with immune checkpoint inhibitors in metastatic CRC.
Insights
Oncolytic peptides DTT-205 and DTT-304 show promise for colorectal cancer (CRC) treatment, inducing tumor regression and long-lasting immune responses. DTT-205 demonstrated superior safety and efficacy, suggesting potential for combination therapies in metastatic CRC.
Area of Science:
- Oncology
- Immunology
- Drug Development
Background:
- Oncolytic peptides offer a novel cancer treatment strategy, particularly for non-immunogenic colorectal cancer (CRC).
- These peptides induce immunogenic cell death, stimulating long-lasting anticancer immune responses.
Purpose of the Study:
- To evaluate the efficacy and safety of oncolytic peptides DTT-205 and DTT-304 in preclinical colorectal cancer models.
- To assess the systemic effects and potential for preventing metastasis after treatment.
Main Methods:
- Intratumoral injection of DTT-205 and DTT-304 into murine CRC cell lines (CT26, MC38).
- Monitoring tumor regression, animal survival, and systemic immune response via rechallenge experiments.
- Assessing hemodynamic parameters in rats to evaluate peptide safety.
Main Results:
- Complete tumor regression was achieved in most animals treated with DTT-205 and DTT-304.
- Treated animals showed significant protection against liver metastases upon rechallenge compared to naïve animals.
- DTT-205 exhibited a better safety profile with less hemodynamic impact than DTT-304 and demonstrated broad in vitro activity.
Conclusions:
- Oncolytic peptides DTT-205 and DTT-304 are effective in preclinical CRC models, inducing tumor regression and systemic immunity.
- DTT-205 is a promising candidate for further drug development due to its efficacy and safety.
- These peptides hold potential for combination therapy with immune checkpoint inhibitors in metastatic CRC.
