Vaccination In Multiple Myeloma Research Articles

Immune dysfunction prior to and during vaccination in multiple myeloma: a case study based on COVID-19

Infection is the leading cause of death in multiple myeloma (MM). However, the cellular composition associated with immune dysfunction is not defined. We analyzed immune profiles in the peripheral blood of patients with MM (n = 28) and B-cell chronic lymphoproliferative disorders (n = 53) vs. health care practitioners (n = 96), using multidimensional and computational flow cytometry. MM patients displayed altered distribution of most cell types (41/56, 73%), particularly within the B-cell (17/17) and T-cell (20/30) compartments. Using COVID-19 as a case study, we compared the immune response to vaccination based on 64,304 data points generated from the analysis of 1099 longitudinal samples. MM patients showed limited B-cell expansion linked to lower anti-RBD and anti-S antibody titers after the first two doses and booster. The percentages of B cells and CD4+ T cells in the blood, as well as the absolute counts of B cells and dendritic cells, predicted vaccine immunogenicity at different time points. In contrast with the humoral response, the percentage and antigen-dependent differentiation of SARS-CoV-2-specific CD8+ T cells was not altered in MM patients. Taken together, this study defined the cellular composition associated with immune dysfunction in MM and provided biomarkers such as the B-cell percentage and absolute count to individualize vaccination calendars.

438 - The Efficacy of Measles, Mumps, Rubella (MMR) Vaccination in Multiple Myeloma (MM) Patients after Hematopoietic Stem Cell Transplantation (HSCT)

438 - The Efficacy of Measles, Mumps, Rubella (MMR) Vaccination in Multiple Myeloma (MM) Patients after Hematopoietic Stem Cell Transplantation (HSCT)

Serological Response to Vaccination after Autologous Transplantation for Multiple Myeloma Is Associated with Improved Progression-Free and Overall Survival

Revaccination after autologous hematopoietic cell transplantation (AHCT) is recommended in post-HCT survivorship guidelines to restore humoral immunity. Data on seroconversion after AHCT and vaccination in multiple myeloma (MM) patients are limited. We investigated the feasibility and effectiveness of vaccination post-AHCT and analyzed the restoration of humoral immunity and patient prognosis. Anti-pathogen titers were measured within a median of 2 days before and 96 days after AHCT and following revaccination in 139 MM patients who had a first AHCT from 2013 to 2016. Most (84%) patients received at least one dose of any planned vaccines. High-dose melphalan with AHCT restored measurable immunity in 18% of patients. In an additional >60% of patients, seroconversion occurred after vaccination; however, despite vaccination, 20% of patients remained seronegative for most pathogens. Attainment of MM complete response post-AHCT was associated with higher rates of seroconversion which yielded significantly longer progression-free and overall survival. Our study demonstrates the feasibility of post-AHCT vaccination, supporting measurement of post-vaccination titers to determine which patients should be considered for antimicrobial prophylaxis, as seroconversion does not occur in all patients. Titer seroconversion is a potential indicator of the immunological effects of AHCT, with restoration of humoral immunity demonstrating improved survival.

Response to pneumococcal vaccination in multiple myeloma.

Background Streptococcus pneumoniae infection causes morbidity and mortality in multiple myeloma patients. Pneumococcal vaccination is commonly given to immunocompromised myeloma patients; however response data are sparse. Here, we present longitudinal response data to pneumococcal vaccination in multiple myeloma patients.MethodTwenty‐eight multiple myeloma patients were included, 25 of whom were newly diagnosed. All the patients received two vaccines Prevnar13® and Pneumo23®. Serotype‐specific IgG was measured by ELISA for all 23 vaccine serotypes at baseline, and then sequentially at different time points postvaccination until treatment ended. Response to vaccination is available for 20 patients. The primary endpoint was the incidence rate of patients who obtained an isotype response serum concentration after vaccination. Secondary endpoints included detailed isotype increase, time to first increase, further assessment of a decreased anti‐pneumococcal serum concentrations following treatment including autologous stem cell transplantation (ASCT), rate of infection with a special attention to pneumococcal infection.ResultsThe median age was 66 years and the male to female ratio was 0.6. Anti‐pneumococcal capsular polysaccharide (anti‐PCP23) IgG, IgG2, IgA, and IgM responses were detected within 1 week postvaccination. Response to at least one subtype of antibody was obtained in 85% (n = 17) of patients, for at least two subtypes in 65% (n = 13), for at least three subtypes in 55% (n = 11), and 2 patients responded to all four subtypes. The median increase in the concentration of anti‐PCP23 isotypes was threefold following vaccination, with the highest increase observed when Pneumo23® was given more than 30 days after Prevnar13®. The anti‐pneumococcal geometric mean concentration decreased significantly for all subtypes over time independently of treatment approaches.ConclusionMyeloma has the ability to demonstrate a response to pneumococcal vaccine, independently of preexisting hypogammaglobulinemia and possibly of treatment‐induced immunodepression. We also observed a drop in the serum response overtime and following autologous transplantation. Further studies in larger sample are needed to understand the benefit of vaccination strategies in these patients.

Multiple Myeloma Vaccination Patterns in a Large Health System: A Pilot Study.

Common reasons for hospitalization and death in patients with multiple myeloma (MM) are infections. As patients with MM are living longer and are treated with immunomodulatory drugs, there is a need to immunize against vaccine-preventable diseases and ultimately determine the efficacy of these vaccines. We evaluated vaccination practice patterns in MM patients at our health system using electronic medical records and data analytics. This institutional review board-approved study retrospectively reviewed patients with MM who visited the health system from May 2012 to May 2014. Data collected included demographics, influenza vaccination (FV) and pneumonia vaccination (PV) history, hospitalization episodes and associated costs, and duration of survival. Patients were considered PV-positive if vaccinated within 5 years prior to study. FV was defined as optimal (two FV in 2012-2014), suboptimal (one FV in 2012-2014) or none (in 2012-2014). Of 411 MM patients, 55% were male and 85% Caucasian. Nearly 58% received PV in the past 5 years. FV was 15% optimal, 52% suboptimal and 33% none. A total of 444 hospitalizations involving 204 patients were observed over 2-year follow-up. More than $23 million was incurred from hospitalizations in the 2-year study period. There was no statistically significant difference in all-cause hospitalization and overall survival by FV and PV status. Despite recommendations of vaccination in multiple myeloma, our cohort had low rates of influenza and pneumonia vaccination. FV and PV status did not show any significant association with additional hospitalization or overall survival in this pilot study. Future prospective studies are needed to ascertain the immunological and clinical efficacy and effectiveness of these vaccines in immunosuppressed patients.

A Novel Dendritic Cell-Derived Vaccine in Multiple Myeloma

Introduction: Despite recent advances in the treatment of multiple myeloma (MM), curative outcomes remain elusive with standard therapies. MM is characterized by immune dysregulation and a loss of tumor-associated T cell surveillance contributing to disease evolution. Cancer vaccines have emerged as a promising immunotherapeutic strategy that seeks to reestablish anti-tumor immunity through the effective presentation of tumor associated antigens in the context of positive costimulation and activation signals. DCOne is a cell based tumor vaccine derived from an acute myelogenous leukemia cell line, differentiated toward a dendritic cell (DC) phenotype (DCPrime, Netherlands). DCOne strongly expresses WT-1, PRAME, RHAMM, survivin, and MUC-1. Since MM cells commonly express these tumor-associated antigens as well, we explored the efficacy of DCOne in inducing myeloma-specific immunity.Methods/Results: We first investigated the capacity of DCOne to polarize T cells toward an activated phenotype. Peripheral blood mononuclear cells (PBMCs) derived from MM patients were cultured in the presence or absence of DCOne and pulsed with whole cell DCOne lysate 24 hours prior to analysis. Intracellular levels of IFN-γ and perforin in CD8+ T cells and intracellular levels of IL-10 in CD4+ T cells were assessed via FACS analysis. Following 10 days of co-culture, we observed an increased percentage of CD8+ IFN-γ+ T cells and an increased percentage of CD8+ perforin+ T cells in PBMCs co-cultured with DCOne versus those not co-cultured with DCOne (10.8% versus 3.3%, p=0.02, n=11 and 6.6% versus 1.7%, p=0.045, n=10, respectively). In contrast, exposure of PBMCs to DCOne did not alter the percentage of CD4+ IL-10+ T cells (p=0.53, n=8). Given the observed increase in IFN-γ- and perforin-positive CD8+ T cells after co-culture of MM PBMCs with DCOne, we investigated whether CD8+ T cells co-cultured with DCOne exhibited enhanced killing of autologous tumor cells in a standard cytotoxic T lymphocyte (CTL) assay measuring Granzyme B activity by FACS analysis. DCOne potently induced CTL-mediated killing of autologous MM cells as determined by an increased percentage of CD8+ Granzyme B+ cells in stimulated versus control cells (27.4% versus 12.5%, p=0.05, n=3).We next investigated the mechanism of action by which DCOne elicited a MM-specific response. We postulated that the allogeneic cell line would induce immune activation in part through the transfer of antigen to PBMC-derived antigen presenting cells; these antigen presenting cells would in turn be capable of eliciting response via MHC restricted presentation of antigen to autologous T cell populations. Consistent with this hypothesis, we demonstrated that 32% of patient-derived PBMCs exhibited uptake of DCOne RNA following co-culture (n=3). Uptake of DCOne RNA by patient-derived PBMCs was completely abrogated with Transwell separation. Next, we examined how patient-derived PBMCs take up DCOne antigens. Using Western Blot analysis, we found that MUC-1 and survivin are expressed in extracellular vesicles (EVs) derived from DCOne lysate. Thus, we conclude that DCOne antigens are trafficked via EVs secreted by the DCOne parent cell, whereupon they are taken up by MM patient-derived PBMCs.Conclusion: In conclusion, when cultured in vitro with MM patient-derived PBMCs, DCOne results in increased IFN-γ- and perforin-positive CD8+ T cells, as well as induction of autologous tumor killing by these cells. DCOne RNA is taken up by MM patient-derived PBMCs and trafficked to the extracellular environment via EVs. DCOne demonstrates in vitro efficacy as an "off-the-shelf" strategy for stimulating MM-specific immunity. A clinical trial is being planned. DisclosuresKruisbeek:DCPrime: Employment, Other: Founder, CSO, and CEO of DCPrime. Van Wetering:DCPrime: Employment. Arnason:Gilead: Consultancy. Rosenblatt:DCPrime: Research Funding; BMS: Research Funding; Astex: Research Funding. Avigan:Astex: Research Funding; DCPrime: Research Funding.

Vaccination in Multiple Myeloma: Review of Current Literature.

Multiple myeloma is a cancer of the immune system. Infection is a major cause of morbidity and mortality in patients with multiple myeloma. Some of these infections are preventable by vaccines available to the general population. However, little is known about the clinical effectiveness of these vaccines in patients with multiple myeloma, and the cellular and humoral immune response to vaccination has not been well characterized, especially in conjunction with modern myeloma therapies. The present report reviews the basics of multiple myeloma and the immune system, the available evidence on the immunologic response of patients with multiple myeloma after vaccination, and current practice recommendations regarding specific vaccines. Understanding the immune response to vaccines could help us understand how immuno-oncology-based therapies work in multiple myeloma and provide future directions for research.

MUC1-2VNTR DNA Vaccine Induces Immune Responses in Mouse Model with Multiple Myeloma

To investigate the humoral and cellular immune responses induced by MUC1-2VNTR DNA vaccine in multiple myeloma (MM) tumor-bearing mice. In vitro, multiple myeloma cells were transfected by plasmid pcDNA3.1-2VNTR/myc-hisB with Lipofectamine2000. The above-mentioned mouse myeloma cells were inoculated subcutaneously into female BALB/c mice for establishing tumor-bearing animal models. These female BALB/c mice were immunized with pcDNA-2VNTR/myc-hisB or pcDNA/myc-hisB. The cytotoxic T lymphocyte (CTL) activity was detected by the LDH method and the spleen lymphocyte proliferation activity was detected by CCK-8 method. After immunization of BALB/c tumor-bearing mice with recombinant plasmid for 25 days, the tumor mass (0.5605 ± 0.2065 g) was significantly lighter than that in the empty plasmid control group (1.521 ± 0.6985 g) (P < 0.01) and the control group (1.5315 ± 0.5425 g) (P < 0.01). The difference of tumor mass was not statislically significant between empty plasmid control group (1.521 ± 0.6985 g) and the control group (1.5315 ± 0.5425 g) (P > 0.05). The CTL and NK cell activity was significantly higher in the group of intramuscular injection with recombinant plasmid than that in control group. The spleen lymphocyte proliferation was statistically significantly increased after being immunized with recombinant plasmid pcDNA3.1-2VNTR/myc-hisB, compared with empty vector (P < 0.01). The results showed that MUC1-2VNTR gene immunization could induce anti-tumor effect in MM tumor-bearing mice. MUC1-2VNTR DNA immunization can elicit both humoral and cellular tumor specific immune response to multiple myeloma in MM tumor-bearing mice. It suggested that the MUC1-2VNTR DNA vaccine may be a potential treatment measure for patients with MM.

Results of a Phase Ii Clinical Trial with Id-Protein-Loaded Dendritic Cell Vaccine in Multiple Myeloma: Encouraging or Discouraging?

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.

Novel tyrosine mutant recombinant adeno-associated viral (rAAV) transduction of dendritic cells (DCs) as a step towards therapeutic vaccination in multiple myeloma (MM)

Batchu, Ramesh B. PhD; Gruzdyn, Oksana BA; Weaver, Donald MD, FACS; Gruber, Scott A. MD, MBA, PhD, FACS Author Information

Blockade of B7H1 by Monoclonal Antibodies Enhances Therapeutic Immunity of DKK1 Vaccine in Multiple Myeloma

Abstract 2941Current approaches for vaccination and immunotherapy are often capable of eliciting strong T-cell responses against tumor antigens. However, negative regulatory mechanisms within the tumor microenvironment inhibit antitumor T-cell function, leading to evasion from immune attack. One inhibitory mechanism is upregulation of programmed death-ligand 1 (PD-L1/B7H1) expressed on tumor or stromal cells, which binds to programmed death-1 (PD-1) on activated T cells. PD-1 and B7H1 engagement results in diminished antitumor T-cell responses and correlates with poor outcome in murine and human cancers.To cure mice with large tumor burdens by administering tumor vaccines, we hypothesized that it is necessary not only to enhance the immunogenicity of the vaccines, but also to target the suppressive tumor microenvironment and break immune suppression on effector cells. Therefore, we explored combinational treatments in a myeloma setting by using vaccination and anti-B7H1 blocking mAbs to enhance clinical efficacy of cancer vaccines. To establish mouse tumor models for evaluation of tumor-associated B7H1 in the inhibition of T-cell immunity, first, we examined the expression of B7H1 in four murine myeloma cell lines that originated from Balb/c mice. Results showed that all the myeloma cells expressed a negative T-cell costimulatory molecule B7H1, and blocking surface B7H1 by using a specific mAb (M5H1) enabled tumor-specific CTLs from vaccinated mice to be more efficient at lysing the tumor cells. Thus these results suggest that B7H1 on tumor cells and PD-1 on T cells may form a B7H1/PD-1 molecular shield to prevent lysis by T cells and actively inhibit the cytolytic function of tumor-specific CTLs by expressing B7H1. Next, we evaluated the therapeutic efficacy of DKK1-DNA vaccine in mice with established myeloma. In these experiments, DKK1-DNA vaccine plus CpG was used as a standard vaccine. Anti-B7H1 (M5H1) mAb was used to block negative T-cell signaling in mice receiving DKK1-DNA vaccination. Balb/c mice were first inoculated subcutaneously with the myeloma cells (1 million cells per mouse). Ten days after tumor inoculation, mice were immunized with three injections of the vaccines on days 10, 14, and 17 after tumor inoculation. Mice were also injected intraperitoneally with B7H1 (200 μg per mouse per treatment) on days 1, 4, 7, and 10 following the first vaccination. Mice receiving injections of PBS, isotype IgG (200 μg per mouse per treatment), or CpG- (50 μg per mouse per treatment) alone were used as controls. Results show that mice receiving DKK1-DNA vaccine (plus CpG) together with B7H1 induced more robust tumor growth inhibition (P < 0.01, compared with PBS control mice). The survival of DKK1-CpG vaccine- and vaccine plus B7H1 antibody-treated mice were 60% and 80%, respectively. Thus, our data showed that B7H1 blocking mAbs can further enhance the therapeutic efficacy of the vaccine.Finally, we investigated the mechanism of therapeutic efficacy of vaccine enhanced by anti-B7H1 mAbs. Our results showed that the percentages of IL-10-secreting or Foxp3+ Tregs in the spleens and tumors are significantly decreased in mice vaccinated with DKK1 DNA plus CpG in combination with anti-B7H1 antibodies (P < 0.01, compared with mice receiving DKK1 DNA alone or vaccine plus CpG). These results indicate that myeloma cells are able to induce or recruit regulatory T cells, and the beneficial effects of anti-B7H1 mAbs were derived from their ability to reduce the numbers of Tregs in tumor-bearing mice. Taken together, these results support the concept that B7H1/PD-1 forms a molecular shield to prevent destruction by CTLs and implicate new approaches for immunotherapy of human cancers by B7H1 blocking mAbs. Disclosures:No relevant conflicts of interest to declare.

CpG or IFN-α are more potent adjuvants than GM-CSF to promote anti-tumor immunity following idiotype vaccine in multiple myeloma

Idiotype (Id) protein in combination with GM-CSF has been used as vaccines for immunotherapy of patients with myeloma and B-cell tumors and the results have been disappointing. To search for better immune adjuvants to improve the efficacy of Id-based immunotherapy in myeloma, we evaluated and compared the efficacy of vaccination of Id protein in combination with CpG or IFN-α, or GM-CSF as a control, in the 5TGM1 myeloma mouse model. Our results showed that Id vaccine combined with CpG or IFN-α, but not GM-CSF, not only efficiently protected mice from developing myeloma but also eradicated established myeloma. The therapeutic responses were associated with an induction of strong humoral immune responses including anti-Id antibodies, and cellular immune responses including Id- and myeloma-specific CD8+ cytotoxic T lymphocytes (CTLs), CD4+ type-1 T-helper (Th1) cells and memory T cells in mice receiving Id vaccine combined with CpG or IFN-α. Furthermore, Id vaccine combined with CpG or IFN-α induced Id- and tumor-specific memory immune responses that protected surviving mice from tumor rechallenge. Thus, our study clearly shows that CpG or IFN-α are better immune adjuvants than GM-CSF. This information will be important for improving the strategies of Id-based immunotherapy for patients with myeloma and other B-cell tumors.

Partial T Cell-Depleted Allogeneic Stem Cell Transplantation following Reduced-Intensity Conditioning Creates a Platform for Immunotherapy with Donor Lymphocyte Infusion and Recipient Dendritic Cell Vaccination in Multiple Myeloma

Allogeneic stem cell transplantation (SCT) in multiple myeloma (MM) may induce a curative graft-versus-myeloma (GVM) effect. Major drawback in unmanipulated reduced-intensity conditioning (RIC) SCT is the risk of severe and longstanding graft-versus-host-disease (GVHD). This study demonstrates that transplantation with a partial T cell-depleted graft creates a platform for boosting GVM immunity by preemptive donor lymphocyte infusion (DLI) and recipient dendritic cell (DC) vaccination, with limited GVHD. All 20MM patients engrafted successfully. Chimerism analysis in 19 patients evaluable at 3 months revealed that 7 patients were complete donor, whereas 12 patients were mixed chimeric. Grade II acute GVHD (aGVHD) occurred in 7 patients (35%) and only 4 patients (21%) developed chronic GVHD (cGVHD). Fourteen patients received posttransplantation immunotherapy, 8 preemptive DLI, 5 patients both DLI and DC vaccination, and 1 patient DC vaccination only. DC vaccination was associated with limited toxicity, and none of these patients developed GVHD. Importantly, overall treatment-related mortality (TRM) at 1 year was low (10%). Moreover, the overall survival (OS) is 84% with median follow-up of 27 months, and none of the patients died from progressive disease. These findings illustrate that this novel approach is associated with limited GVHD and mortality, thus creating an ideal platform for adjuvant immunotherapy.

Current Vaccination Strategies for the Treatment of B-Cell Lymphoma and Multiple Myeloma

Therapeutic vaccines have been developed to induce immune responses capable of eradicating lymphoma and myeloma tumors. Most of these vaccines target the immunoglobulin idiotype (Id) as a tumor-specific antigen. Phase I/II clinical trials of Id vaccination in lymphoma demonstrated that some lymphoma patients could mount immune responses that were correlated with a favorable clinical outcome. These encouraging results initiated phase III trials of Id vaccination in lymphoma, the results of which have been recently released. Disappointingly, only one of three phase III studies achieved the primary end point of progression-free survival. Detailed analysis of these results is awaited to help identify factors that determine clinical efficacy of Id vaccination as reflected in the three trials. Unlike lymphoma, studies of Id vaccination in multiple myeloma have yielded far less evidence of clinical benefit. Although Id vaccines induce immune responses in myeloma patients, their efficacy is insufficient to provide a clear clinical benefit. Strategies to improve lymphoma and myeloma vaccines are currently tested with an emphasis on optimization of antigen delivery and presentation and modulation of the immune system toward enhancement of T-cell function. Despite many hurdles yet to overcome, it is hoped that newly developed strategies that augment both immune and clinical responses will allow effective vaccination resulting in tumor eradication.

Long-term follow-up of idiotype vaccination in human myeloma as a maintenance therapy after high-dose chemotherapy.

The aim of this work was to evaluate the long-term immunological and clinical impact of idiotype (Id) vaccination in multiple myeloma (MM) patients in first remission after high-dose chemotherapy. A total of 15 patients received a series of subcutaneous (s.c.) injections of autologous Id, conjugated to keyhole limpet hemocyanin (KLH) and in association with low doses of GM-CSF. The median duration of follow-up was 110 months from diagnosis. The vaccine induced immune responses that lasted almost 2 years after the end of treatment. Antibody responses included anti-KLH IgM and IgG (90% of patients), anti-KLH IgE (30%), anti-GM-CSF IgG (20%), anti-Id IgG (20%), and anti-Id IgE (30%). Id-specific delayed type hypersensitivity skin tests were positive in 85% of tested patients. Following vaccination, a progressive recovery of T-cell receptor (TCR) diversity was observed and the loss of oligoclonality was significantly correlated with the remission duration. Although Id/KLH conjugates did not eliminate the residual tumor burden, the median progression-free survival, and overall survival were 40 and 82 months, respectively. A retrospective case-matched analysis showed similar results in patients treated with IFN-alpha alone or in association with steroids. This vaccine formulation can overcome Id-specific immune tolerance by inducing clinical responses that are worthy of further investigation.

Idiotypic protein-pulsed dendritic cell vaccination in multiple myeloma

Idiotypic protein (Id) produced by myeloma cells is clone-specific and may be a suitable tumor-specific antigen for immune targeting. Advances in dendritic cell (DC) technology suggest the opportunity for using this potent antigen presentation system to deliver myeloma Id to the autologous host to elicit anti-tumor immune responses. We have generated DCs from adherent PBMCs from 6 patients with IgG myeloma. These cells were pulsed with the autologous Id and a control vaccine, KLH, and re-infused i.v. back to the patients on 3 separate occasions. Immune responses to KLH and autologous Id were measured and clinical responses monitored. We found that all treatments were well tolerated without any side effects. All patients developed both B- and T-cell responses to KLH, suggesting the integrity of the host immune system to mount immune responses to an antigen delivered using our vaccination strategy. Id-specific responses were also observed. PBMC proliferative responses to Id were observed in 5 of the 6 patients following treatment. In 2 patients, the responses were associated with the production of IFN-gamma. There were also increases in cytotoxic T-cell precursor frequencies for Id-pulsed autologous targets in 3 patients. B-cell responses characterized by the production of anti-Id IgM occurred in 3 and anti-Id IgG in 4 of the 5 evaluated patients. In 1 patient, a modest (25%) but consistent drop in the serum Id level was observed. Id-pulsed DC vaccination can therefore elicit potentially useful anti-myeloma immune responses in patients with multiple myeloma.

Idiotypic protein‐pulsed dendritic cell vaccination in multiple myeloma

Idiotypic protein (Id) produced by myeloma cells is clone-specific and may be a suitable tumor-specific antigen for immune targeting. Advances in dendritic cell (DC) technology suggest the opportunity for using this potent antigen presentation system to deliver myeloma Id to the autologous host to elicit anti-tumor immune responses. We have generated DCs from adherent PBMCs from 6 patients with IgG myeloma. These cells were pulsed with the autologous Id and a control vaccine, KLH, and re-infused i.v. back to the patients on 3 separate occasions. Immune responses to KLH and autologous Id were measured and clinical responses monitored. We found that all treatments were well tolerated without any side effects. All patients developed both B- and T-cell responses to KLH, suggesting the integrity of the host immune system to mount immune responses to an antigen delivered using our vaccination strategy. Id-specific responses were also observed. PBMC proliferative responses to Id were observed in 5 of the 6 patients following treatment. In 2 patients, the responses were associated with the production of IFN-γ. There were also increases in cytotoxic T-cell precursor frequencies for Id-pulsed autologous targets in 3 patients. B-cell responses characterized by the production of anti-Id IgM occurred in 3 and anti-Id IgG in 4 of the 5 evaluated patients. In 1 patient, a modest (25%) but consistent drop in the serum Id level was observed. Id-pulsed DC vaccination can therefore elicit potentially useful anti-myeloma immune responses in patients with multiple myeloma. Int. J. Cancer 83:215–222, 1999. © 1999 Wiley-Liss, Inc.