Randomized, placebo-controlled, double-blinded chemoimmunotherapy clinical trial in a pet dog model of diffuse large B-cell lymphoma.

Abstract

PURPOSE:

Active immunotherapy is a promising antitumoral strategy; however its use in combination with chemotherapy in dogs with large B-cell lymphoma (DLBCL) remains largely untested. Heat shock proteins (HSP) bind the small peptides they chaperone (HSPPC), allowing for immunization of the host against a large repertoire of tumor-associated antigens. Hydroxylapatite vehicles HSPPCs and acts as an immunologic adjuvant. The aim of this study was to show that an autologous vaccine with hydroxylapatite and tumor-derived HSPPCs is safe and therapeutically effective in dogs with DLBCL.

EXPERIMENTAL DESIGN:

Nineteen dogs with naturally occurring DLBCL were entered into a prospective randomized placebo-controlled double-blinded trial of HSPPCs-hydroxylapatite plus chemotherapy versus chemotherapy alone. Endpoints included time to progression (TTP), lymphoma-specific survival (LSS), and incidence of toxicoses.

RESULTS:

Median first TTP after randomization to the vaccine arm was 304 days versus 41 days for the control arm (P = 0.0004). There was also a statistically significant difference in duration of second remission between the two groups (P = 0.02). Median LSS was 505 days for the vaccinated dogs versus 159 days for the unvaccinated dogs (P = 0.0018). Six vaccinated dogs achieved molecular remission, as shown by clonal immunoglobulin H (IgH) rearrangement. Toxicoses were comparable between the two treatment arms.

CONCLUSIONS:

The results of this trial demonstrate that the autologous vaccine tested here is safe and efficacious in prolonging TTP and LSS in dogs with DLBCL when used in combination with dose-intense chemotherapy. On the basis of these results, additional evaluation of this novel therapeutic strategy is warranted in human DLBCL.

• Authors: Laura Marconato, Patrick Frayssinet, Nicole Rouquet, Stefano Comazzi, Vito Ferdinando Leone, Paola Laganga, Federica Rossi, Massimo Vignoli, Lorenzo Pezzoli, Luca Aresu
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 20 Issue 3 Pg. 668-77 (Feb 01 2014) ISSN: 1557-3265 [Electronic] United States
• PMID: 24300788 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: ©2013 AACR.

Chemical References

• Adjuvants, Immunologic
• Antigens, Neoplasm
• Antineoplastic Agents
• Cancer Vaccines
• Heat-Shock Proteins
• Durapatite

Topics

• Adjuvants, Immunologic (therapeutic use)
• Animals
• Antigens, Neoplasm (immunology, therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Cancer Vaccines (therapeutic use)
• Dog Diseases (therapy)
• Dogs
• Double-Blind Method
• Durapatite (immunology, therapeutic use)
• Heat-Shock Proteins (immunology, therapeutic use)
• Lymphoma, Large B-Cell, Diffuse (therapy, veterinary)