I came across this research abstract from earlier this year, and I was wondering if anyone knows more about the technique the researchers used in the trial. Is it being tested here in the U.S. or elsewhere? Is it being developed further?
Even though the results of the trial were not particularly "stunning", they seem promising and worth building upon.
Thanks!
Neoplasma. 2012;59(4):440-9.
Efficacy and safety of Id-protein-loaded dendritic cell vaccine in patients with multiple myeloma--phase II study results.
Zahradova L, Mollova K, Ocadlikova D, Kovarova L, Adam Z, Krejci M, Pour L, Krivanova A, Sandecka V, Hajek R.
Source
Department of Internal Medicine-Hematooncology, University Hospital Brno and Masaryk University Brno, Jihlavska 20, 625 00, Brno, Czech Republic.
Abstract
In a phase II clinical study, pretreated multiple myeloma patients with relapsing or stable disease received autologous anticancer vaccine containing dendritic cells loaded with Id-protein. Patients received a total of 6 vaccine doses intradermally in monthly intervals. No clinical responses were observed. During the follow-up with a median of 33.1 months (range: 11-43 months), the disease remained stable in 7/11 (64%) of patients. Immune responses measured by ELISpot were noted in 3/11 (27%) and DTH skin test for Id-protein was positive in 8/11 (73%) of patients; out of those, 1/11 (9%) and 5/11 (46%), respectively, had preexisting immune response to Id-protein before the vaccination began. Outcomes were compared to those of a control group of 13 patients. A trend to lower cumulative incidence of progression in the vaccinated group was observed at 12 months from the first vaccination (p= 0.099). More patients from the control group compared to vaccinated patients required active anticancer therapy [4/11 (36%) vs. 8/13 (62%)]. Vaccines based on dendritic cells loaded with Id-protein are safe and induce specific immune response in multiple myeloma patients. Our results suggest that the vaccination could stabilize the disease in approximately two-thirds of patients. Keywords: dendritic cells, immunotherapy, anticancer vaccines, Id-protein, multiple myeloma.
Link to abstract (and option to purchase full-text article):
http://tinyurl.com/bt2hoz8
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Re: Dendritic cell vaccine for multiple myeloma
Actually, just today I saw an abstract on PubMed talking about the study you mention: the title speaks for itself -- but the data suggest promise for at least some patients.
Results of a Phase II clinical trial with Id-protein-loaded dendritic cell vaccine in multiple myeloma: encouraging or discouraging?
Garcia-Marquez MA, Wennhold K, Draube A, von Bergwelt-Baildon M.
SourceCologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne, Kerpener Str. 62, D-50924 Cologne, Germany.
Abstract
Evaluation of: Zahradova L, Mollova K, Ocadlikova D et al. Efficacy and safety of Id-protein-loaded dendritic cell vaccine in patients with multiple myeloma - Phase II study results. Neoplasma 59(4), 440-449 (2012). Recently gained insight into the role of dendritic cells (DCs) as APCs has attracted the attention of many researchers who hope to use them as a tool in immunotherapy for the induction of tumor-specific immunity in cancer settings. Despite high expectations, in multiple myeloma patients the results of DC-based vaccines in terms of clinical response have been disappointing. The findings of Zahradova et al. in a Phase II clinical trial with multiple myeloma patients corroborated these results. Although no clinical responses were observed, the investigators induced immunity after vaccination with Id-protein-loaded DC vaccine in some patients. These immunological results showed a trend towards a longer duration of stable disease in those patients that received the vaccination. Moreover, this study showed that Id-protein-loaded DC vaccines are safe and nontoxic and that they are able to induce immunity in some patients. Therefore, standardization of vaccination protocols appears to be the key to achieving a better clinical outcome.
Results of a Phase II clinical trial with Id-protein-loaded dendritic cell vaccine in multiple myeloma: encouraging or discouraging?
Garcia-Marquez MA, Wennhold K, Draube A, von Bergwelt-Baildon M.
SourceCologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne, Kerpener Str. 62, D-50924 Cologne, Germany.
Abstract
Evaluation of: Zahradova L, Mollova K, Ocadlikova D et al. Efficacy and safety of Id-protein-loaded dendritic cell vaccine in patients with multiple myeloma - Phase II study results. Neoplasma 59(4), 440-449 (2012). Recently gained insight into the role of dendritic cells (DCs) as APCs has attracted the attention of many researchers who hope to use them as a tool in immunotherapy for the induction of tumor-specific immunity in cancer settings. Despite high expectations, in multiple myeloma patients the results of DC-based vaccines in terms of clinical response have been disappointing. The findings of Zahradova et al. in a Phase II clinical trial with multiple myeloma patients corroborated these results. Although no clinical responses were observed, the investigators induced immunity after vaccination with Id-protein-loaded DC vaccine in some patients. These immunological results showed a trend towards a longer duration of stable disease in those patients that received the vaccination. Moreover, this study showed that Id-protein-loaded DC vaccines are safe and nontoxic and that they are able to induce immunity in some patients. Therefore, standardization of vaccination protocols appears to be the key to achieving a better clinical outcome.
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Dan D
Re: Dendritic cell vaccine for multiple myeloma
And here is another abstract that just came out, also talking about the hope of cellular immunotherapy and dendritic vaccines:
Immunotherapy. 2012 Oct;4(10):1043-1051.
Evolution of cellular immunotherapy: from allogeneic transplant to dendritic cell vaccination as treatment for multiple myeloma.
Arnason J, Avigan D.
Beth Israel Deaconess Medical Center, Hematologic Malignancies & Bone Marrow Transplantation Program, Harvard Medical School, MA, USA.
Abstract
The promise of cellular therapy as treatment for multiple myeloma is highlighted by the observation that allogeneic transplantation results in durable remissions in a subset of patients. The potency of the graft-versus-myeloma effect is supported by the decreased risk of relapse seen in patients with graft-versus-host disease and disease response following donor lymphocyte infusions. However, the lack of specificity of the alloreactive lymphocytes limits their therapeutic efficacy and results in significant treatment-related morbidity and mortality. A major area of investigation is the development of cancer vaccines to generate myeloma-specific immunity that selectively targets malignant cells while minimizing toxicity to normal tissues. Critical elements required to develop an effective vaccine strategy involve the identification of myeloma-associated antigens, enhancement of antigen presentation, and reversing the immunosuppressive milieu induced by the disease. Dendritic cells are potent APCs that represent an ideal platform for vaccination. Strategies for vaccine design include the loading of individual antigens as well as the use of whole tumor cells as a source of myeloma antigens. Vaccination has been examined in the postautologous transplant setting in which disease cytoreduction and depletion of Tregs is associated with enhanced vaccine response. Recent efforts have also included exploration of immune modulatory agents that target inhibitory pathways to enhance vaccine response and create a more durable antitumor immunity.
Immunotherapy. 2012 Oct;4(10):1043-1051.
Evolution of cellular immunotherapy: from allogeneic transplant to dendritic cell vaccination as treatment for multiple myeloma.
Arnason J, Avigan D.
Beth Israel Deaconess Medical Center, Hematologic Malignancies & Bone Marrow Transplantation Program, Harvard Medical School, MA, USA.
Abstract
The promise of cellular therapy as treatment for multiple myeloma is highlighted by the observation that allogeneic transplantation results in durable remissions in a subset of patients. The potency of the graft-versus-myeloma effect is supported by the decreased risk of relapse seen in patients with graft-versus-host disease and disease response following donor lymphocyte infusions. However, the lack of specificity of the alloreactive lymphocytes limits their therapeutic efficacy and results in significant treatment-related morbidity and mortality. A major area of investigation is the development of cancer vaccines to generate myeloma-specific immunity that selectively targets malignant cells while minimizing toxicity to normal tissues. Critical elements required to develop an effective vaccine strategy involve the identification of myeloma-associated antigens, enhancement of antigen presentation, and reversing the immunosuppressive milieu induced by the disease. Dendritic cells are potent APCs that represent an ideal platform for vaccination. Strategies for vaccine design include the loading of individual antigens as well as the use of whole tumor cells as a source of myeloma antigens. Vaccination has been examined in the postautologous transplant setting in which disease cytoreduction and depletion of Tregs is associated with enhanced vaccine response. Recent efforts have also included exploration of immune modulatory agents that target inhibitory pathways to enhance vaccine response and create a more durable antitumor immunity.
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Dan D
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