Vaccination of metastatic renal cell carcinoma patients with autologous tumour-derived vitespen vaccine: clinical findings

Abstract

The aim of this study was to evaluate the clinical efficacy as determined by time to progression and response rate (RR) of autologous vitespen (formerly HSPPC-96; Oncophage, Antigenics Inc., New York, NY, USA) with and without interleukin-2 (IL-2; Proleukin: Chiron, Emoryville, CA, USA) in stage IV metastatic renal cell carcinoma (RCC) patients undergoing nephrectomy. Eighty-four patients were enrolled on study, and then underwent nephrectomy and harvest of tumour tissue for use in autologous vaccine manufacture. Initial treatment schedule started approximately 4 weeks after surgery and consisted of six injections: once weekly for 4 weeks, then two injections biweekly (vaccines administered at weeks 1, 2, 3, 4, 6, 8), followed by restaging at or around week 10. Patients who had stable or responsive disease continued to receive vaccine, with four more vaccinations biweekly (at weeks 10, 12, 14, 16). Patients who had progressive disease at week-10 evaluation received four consecutive 5-day-per-week courses of 11 × 10 6 U of IL-2 subcutaneously (weeks 10, 11, 12, 13), with four doses of vitespen at 2-week intervals (at weeks 10, 12, 14, 16). At the next evaluation (week 18), patients with a complete response received two further cycles of vitespen (with IL-2 if also received during prior cycle) or until vaccine supply was exhausted. Patients with stable disease or partial response repeated their prior cycle of therapy. Disease progressors who had not yet received IL-2 began IL-2 treatment, and progressors who had already received IL-2 came off study. Of 60 evaluable patients, 2 demonstrated complete response (CR), 2 showed partial response (PR), 7 showed stable disease, and 33 patients progressed. Sixteen patients had unconfirmed stable disease. Two patients who progressed on vaccine alone experienced disease stabilisation when IL-2 was added. Treatment with vitespen did not result in a discernable benefit in the majority of patients with metastatic RCC treated in this study. Use in combination with immunoregulatory agents may enhance the efficacy of vitespen.

Translating Tumor Antigens into Cancer Vaccines

“…Vaccines based on proteins complexed with HSPs, purified from autologous tumors (HSP-protein complex), have been evaluated in clinical trials targeting different cancers. In particular, the immunogenicity and efficacy of HSP-protein complex 96 (HSPPC-96; vitespen) made of tumor peptides associated with the heat shock protein gp96 has been extensively assessed in preclinical and clinical trials for a wide range of cancers, including phase I and II trials in colorectal cancer (110), melanoma (7,138), and renal cell carcinoma (82) and two phase III studies of melanoma and renal cell carcinoma (165,172,197,198). Furthermore, a full-length human papillomavirus type 16 (HPV16) E7 antigen fused to HSP65 from Mycobacterium bovis BCG (HspE7) (33) has been evaluated in a phase II clinical trial, resulting in lesion regression in women with grade III cervical intraepithelial neoplasia (CIN III) (55, 183).…”

Inhibition of Tumor-Induced Myeloid-Derived Suppressor Cell Function by a Nanoparticulated Adjuvant

“…However, even though there is preclinical evidence for the efficacy of cancer vaccine candidates (3)(4)(5)(6), reproducible objective responses in clinical trials are limited (7)(8)(9)(10).…”

Phase II trial of adjuvant immunotherapy with autologous tumor-derived Gp96 vaccination in patients with gastric cancer.

“…Heat shock protein peptide complex 96 can be easily purified from solid tumor and has been safely tested in patients with a variety of solid tumors [11][12][13][14]. In a Phase III trial, no treatment-related grade 3 or 4 adverse events were observed among patients treated with adjuvant HSP vaccine obtained after nephrectomy [3].…”