LTX-315 and adoptive cell therapy using tumor-infiltrating lymphocytes generate tumor specific T cells in patients with metastatic soft tissue sarcoma

ABSTRACT

LTX-315 is an oncolytic peptide that elicits both local and systemic immune responses upon intratumoral injection. In the present pilot trial, we treated patients with metastatic soft tissue sarcoma with the combination of LTX-315 and adoptive T-cell therapy using in vitro expanded tumor-infiltrating lymphocytes. Six heavily pretreated patients were included in the trial and treated with LTX-315 of which four patients proceeded to adoptive T-cell therapy. Overall, the treatment was considered safe with only expected and manageable toxicity. The best overall clinical response was stable disease for 208 days, and in this patient, we detected tumor-reactive T cells in the blood that lasted until disease progression. In three patients T-cell reactivity against in silico predicted neoantigens was demonstrated. Additionally, de novo T-cell clones were generated and expanded in the blood following LTX-315 injections. In conclusion, this pilot study provides proof that it is feasible to combine LTX-315 and adoptive T-cell therapy, and that this treatment can induce systemic immune responses that resulted in stabilization of the disease in sarcoma patients with otherwise progressive disease. Further optimization of the treatment protocol is warranted to increase clinical activity. ClinicalTrials.gov Identifier: NCT03725605

KEYWORDS:

• Adoptive cell therapy
• immunotherapy
• LTX-315
• soft tissue sarcoma
• T-cell therapy
• tumor infiltrating lymphocytes

Acknowledgments

We are deeply grateful to patients and their families for their participation and contribution to this trial. We would also like to thank for the support from all co-workers at the National Center for Cancer Immune Therapy (CCIT-DK) with a special thanks to the technicians responsible for TIL expansion at the GMP facility. Thank you to the Department of Oncology, Herlev Hospital, including attending physicians and nurses; The Department of Orthopedic Surgery, Rigshospitalet; Lytix Biopharma; and NEC Oncoimmunity AS.

Disclosure statement

VS, KC, BS and ØR are employees of Lytix Biopharma. KC, BS, and ØR are shareholders in Lytix Biopharma AS. TC and RS are employees in NEC OncoImmunity AS.

IMS has received honoraria for lectures from Novo Nordisk, MSD, Novartis, Pierre Fabre, Sanofi Aventis, BMS, and Takeda. IMS has received consultancy fees from IO Biotech, MSD, Novartis, Pierre Fabre, and TILT Biotherapeutics. IMS institution has received research grants from BMS, IO Biotech, Adaptimmune, Lytix biopharma, Evaxion Biotech, TILT Biotherapeutics, Enara Bio, and Asgard Therapeutics. IMS is shareholder and co-founder of the biotech company IO Biotech ApS.

TJM has received honoraria for a lecture from BMS.

MN has received travel reimbursement from Lytix Biopharma.

Data availability statement

The data that support the findings of this study are available from the corresponding author, [author initials], upon reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2023.2290900

Additional information

Funding

This clinical trial was funded by Lytix Biopharma with support from Norwegian Research Council (Grant number 269814 (Skattefunn 306724), Permides (EU grant VR 102587)