Discovery of a 9-mer Cationic Peptide (LTX-315) as a Potential First in Class Oncolytic Peptide
Bengt Erik Haug1,2, Ketil André Camilio1,3, Liv Tone Eliassen1
1Lytix Biopharma AS , Sykehusveien 21, NO-9294 Tromsø, Norway.
Abstract:
Oncolytic immunotherapies represent a new promising strategy in the treatment of cancer. In our efforts to develop oncolytic peptides, we identified a series of chemically modified 9-mer cationic peptides that were highly effective against both drug-resistant and drug-sensitive cancer cells and with lower toxicity toward normal cells. Among these peptides, LTX-315 displayed superior anticancer activity and was selected as a lead candidate. This peptide showed relative high plasma protein binding abilities and a human plasma half-life of 160 min, resulting in formation of nontoxic metabolites. In addition, the lead candidate demonstrated relatively low ability to inhibit CYP450 enzymes. Collectively these data indicated that this peptide has potential to be developed as a new anticancer agent for intratumoral administration and is currently being evaluated in a phase I/IIa study.
Insights
Chemically modified peptides show promise as novel oncolytic immunotherapies. LTX-315, a lead candidate, effectively targets cancer cells with reduced toxicity and is advancing to clinical trials.
Area of Science:
- Oncology
- Immunotherapy
- Peptide Therapeutics
Background:
- Oncolytic immunotherapies offer a novel strategy for cancer treatment.
- Development of effective and safe anticancer agents remains a critical need.
Purpose of the Study:
- To identify and develop novel oncolytic peptides for cancer therapy.
- To evaluate the anticancer efficacy and safety profile of lead candidate LTX-315.
Main Methods:
- Chemical modification of 9-mer cationic peptides.
- In vitro evaluation of anticancer activity against drug-resistant and sensitive cancer cells.
- Assessment of toxicity toward normal cells and pharmacokinetic properties of LTX-315.
Main Results:
- Identified chemically modified peptides with high efficacy against various cancer cell types.
- LTX-315 demonstrated superior anticancer activity and lower toxicity compared to other candidates.
- LTX-315 exhibited favorable plasma protein binding, a half-life of 160 minutes, and non-toxic metabolites.
- LTX-315 showed low inhibition of CYP450 enzymes.
Conclusions:
- LTX-315 is a promising lead candidate for oncolytic immunotherapy.
- The peptide's favorable pharmacokinetic and safety profile supports its development for intratumoral administration.
- LTX-315 is currently undergoing Phase I/IIa clinical evaluation.
