Abstract
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. 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. 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. 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.
Highlights
IntroductionNon-Hodgkin lymphoma is the fifth leading cause of cancer-related deaths in people in the United States [1], and for more than 25 years, an anthracycline-based multidrug chemotherapy regimen has been the gold standard for the treatment of diffuse large B-cell lymphoma (DLBCL)
The results of this trial demonstrate that the autologous vaccine tested here is safe and efficacious in prolonging time to progression (TTP) and lymphoma-specific survival (LSS) in dogs with diffuse large B-cell lymphoma (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
Summary
Non-Hodgkin lymphoma is the fifth leading cause of cancer-related deaths in people in the United States [1], and for more than 25 years, an anthracycline-based multidrug chemotherapy regimen has been the gold standard for the treatment of diffuse large B-cell lymphoma (DLBCL). This subgroup is dismal, with a median survival time of 6 months or less, indicating that there is a clinical spectrum of sensitivity to the standard treatment [3]. DLBCL is the most common subtype of canine lymphoma [4, 5], and it shares many features with the human counterpart, including clinical presentation, biologic behavior, tumor genetics, and treatment response [6]. Constitutive and increased NF-kB activities targeting gene expression were recently detected in primary canine DLBCL tissue, rendering the dog a spontaneous model for activated B cell (ABC) DLBCL in people [7, 8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
