Pilot study of intratumoral injection of recombinant heat shock protein 70 in the treatment of malignant brain tumors in children

Abstract

Intratumoral injections of recombinant heat shock protein (Hsp)70 were explored for feasibility in patients with brain tumors. Patients aged 4.5–14 years with untreated newly diagnosed tumors (n=12) were enrolled. After tumor resection, five injections of recombinant Hsp70 (total 2.5 mg) were administered into the resection cavity through a catheter. Before administration of Hsp70 and after the last injection, specific immune responses to the autologous tumor lysate were evaluated using the delayed-type hypersensitivity test. Further, peripheral blood was monitored to identify possible changes in lymphocyte subpopulations, cytokine levels, and the cytolytic activity of natural killer cells. The follow-up period in this trial was 12 months. Intratumoral injections of Hsp70 were well tolerated by patients. One patient had a complete clinical response documented by radiologic findings and one patient had a partial response. A positive delayed-type hypersensitivity test was observed in three patients. In peripheral blood, there was a shift from cytokines provided by Th2 cells toward cytokines of a Th1-cell-mediated response. These data corresponded to changes in lymphocyte subpopulations. Immunosuppressive T-regulatory cell levels were also reduced after injection of Hsp70, as well as production of interleukin-10. The cytolytic activity of natural killer cells was unchanged. The present study demonstrates the feasibility of intratumoral delivery of recombinant Hsp70 in patients with cancer. Further randomized clinical trials are recommended to assess the optimum dose of the chaperone, the treatment schedule, and clinical efficacy.

The role of heat shock protein 70 (Hsp70) in radiation-induced immunomodulation

“…With regard to these promising novel data from pre-clinical studies, a pilot study in children with brain tumors has been initiated. Intratumoral injections of recombinant Hsp70 (up to five times) were well tolerated and one patient out of 12 exhibited a complete clinical response, as documented using radiological imaging [88]. Immunologically, a shift toward an inflammatory Th1 type immune response was observed in the peripheral blood, as was a reduction in the prevalence of Treg cells.…”

Intratumoral immunotherapy for melanoma

“…injections of recombinant heat-shock protein (Hsp)70 were used to treat malignant brain tumors in children; the therapy was safe but not highly effective (one of 12 children had a complete response, and one had a partial response). However, an increased number of Th1 T cells and decreased number of B and Treg cells were seen in the blood of all children in response to Hsp70 treatment [101], suggesting that locally injected Hsp70 may generate a systemic anti-tumor immune response that could be further enhanced with additional immunomodulators such as the T cell checkpoint blockade agents approved for the treatment of metastatic melanoma, anti-CTLA-4 (ipilimumab) and anti-PD-1 (pembrolizumab).…”

Establishing benchmark EQ-5D-3L population health state utilities and identifying their correlates in Gansu Province, China

“…Due to these immunomodulatory activities, HSP70 has been used as a treatment to enhance specific anti-tumour immune responses. In preclinical studies and clinical trials involving brain tumours, hepatocellular carcinoma, colon or lung cancers, intratumoural injection of HSP70, upregulation of HSP70 within the tumour or the use of selective HSP70 peptides for ex vivo stimulation of immune cells, stimulated potent anti-tumour immune responses [22][23][24][25].…”