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Published on: February 16, 2015
LTX-315 and adoptive cell therapy using tumor-infiltrating lymphocytes generate tumor specific T cells in patients
Morten Nielsen1, Tine Monberg1, Vibeke Sundvold2
1National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, Denmark.
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.
Insights
This pilot study combined oncolytic peptide LTX-315 with T-cell therapy for metastatic sarcoma. The combination showed safety and induced systemic immune responses, stabilizing disease in some patients.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Research
Background:
- LTX-315 is an oncolytic peptide with potential for local and systemic immune stimulation.
- Metastatic soft tissue sarcoma remains a challenging condition with limited treatment options.
Purpose of the Study:
- To evaluate the safety and efficacy of combining LTX-315 with adoptive T-cell therapy (ACT) in metastatic soft tissue sarcoma patients.
- To assess the immunogenicity of the combination therapy, including T-cell responses against neoantigens.
Main Methods:
- A pilot trial involving six heavily pretreated metastatic soft tissue sarcoma patients.
- Treatment involved intratumoral injection of LTX-315, with four patients proceeding to ACT using expanded tumor-infiltrating lymphocytes.
- Safety, clinical response, and systemic immune responses (including T-cell reactivity) were monitored.
Main Results:
- The combination therapy was safe and well-tolerated, with manageable toxicity.
- One patient achieved stable disease for 208 days, accompanied by detectable tumor-reactive T cells.
- Three patients demonstrated T-cell reactivity against predicted neoantigens, and de novo T-cell clones emerged post-treatment.
Conclusions:
- Combining LTX-315 with ACT is feasible and can induce systemic immune responses in sarcoma patients.
- This approach showed potential for disease stabilization in patients with progressive metastatic soft tissue sarcoma.
- Further optimization of the treatment protocol is necessary to enhance clinical activity.
