Adoptive T-Cell Therapy May Have Metastatic Cervical Cancer Potential

Tumour-infiltrating T-cell therapy may have efficacy in patients with metastatic cervical cancer

medwireNews: Preliminary results suggest that adoptive T-cell therapy (ACT) targeting tumours expressing high-risk human papillomavirus (HPV) oncoproteins could be effective for the treatment of metastatic cervical cancer.

Three of the nine patients treated with a single infusion of tumour-infiltrating T-cells achieved an objective tumour response, including two complete responses that continued for 15 and 22 months after treatment. A partial response in a third patient lasted for 3 months.

Of note, the complete responses occurred in one patient with Squamous cell carcinoma and in another with adenocarcinoma, both of whom had progressing metastases affecting multiple sites including lymph nodes.

“These results may have important implications for immunotherapy of cervical cancer and for the expanded application of cellular therapy”, write Christian Hinrichs, from the National Cancer Institute in Bethesda, Maryland, USA, and co-authors in the Journal of Clinical Oncology.

The tumour-infiltrating T-cells were selected where possible for reactivity against the HPV-16 or -18 E6 and E7 oncoproteins and given after lymphocyte-depleting chemotherapy, the researchers explain.

Analysis revealed that the three patients with the highest frequency of HPV-reactive T-cells in their infusion were the same patients who achieved an objective response, whereas two patients with no HPV reactivity experienced no tumour response.

“[T]he number of patients in these exploratory studies was small, and the results must be interpreted cautiously”, Christian Hinrichs et al emphasise.

Nevertheless, they note that while patients had minimal, if any, T-cell HPV reactivity before treatment, six patients had an increase in reactivity against E6 and E7 a month after treatment, and again the three patients with the highest reactivity achieved objective responses.

Indeed, all three patients with objective responses had elevated T-cell reactivity for between 2 and 13 months after treatment, indicating “that responding patients experienced prolonged repopulation with the infused HPV-reactive T cells”.

There were no acute or autoimmune adverse events following ACT and most grade 3 or 4 adverse events were associated with lymphocyte depletion.

“ACT is a highly personalized, novel therapeutic approach that may circumvent the inherent limitations of chemotherapy in cervical cancer”, the authors conclude.

“Further study of HPV-[tumour-infiltrating lymphocytes] is warranted.”

Reference

Stevanović S, Draper LM, Langhan MM, et al. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells. J Clin Oncol 2015; Advance online publication 30 March. doi: 10.1200/JCO.2014.58.9093

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