scholarly journals Latest Developments in Cellular Therapy for Multiple Myeloma

2021 ◽  
Vol 16 (2) ◽  
pp. 111
Author(s):  
Tara K Gregory ◽  
Henning Schade ◽  
Jesús G Berdeja ◽  
◽  
◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cellular Therapy

Chimeric antigen receptor T in the treatment of multiple myeloma – state of the art and future directions

2020 ◽  
Vol 51 (3) ◽  
pp. 120-124
Author(s):  
Dominik Dytfeld
Keyword(s):  
Multiple Myeloma ◽  
Chimeric Antigen Receptor ◽  
Cellular Therapy ◽  
New Technology ◽  
Phase 1 ◽  
Antigen Receptor ◽  
New Drugs ◽  
Adoptive Cellular Therapy ◽  
B Cell Maturation ◽  
Complexity Cost

AbstractIn spite of the introduction of several new drugs in the last 10 years, multiple myeloma (MM) remains incurable. Thus, an adoptive cellular therapy using chimeric antigen receptor T (CART), a strategy to increase the frequency of tumor-directed and functionally active T cells targeting antigens present on the cancer cell, might change the treatment in MM as it did in lymphoma and ALL. There are several targets for CART therapy in MM on different levels of development, which are discussed in the manuscript. B-cell maturation antigen (BCMA) being tested in the studies of phase 1–2 is the most promising, but so far CART has not been approved in the cure of MM and remains an experimental approach. The hematological society is facing a new technology which with its potential ability to cure MM, in spite of its complexity, cost, and toxicity, will definitely and soon change the landscape of myeloma in Europe and world-wide.

Emerging Targets and Cellular Therapy for Relapsed Refractory Multiple Myeloma: A Systematic Review

2021 ◽  
Author(s):  
Laeth L George ◽  
Saarang R Deshpande ◽  
Matthew J Cortese ◽  
Ellen K Kendall ◽  
Asmi Chattaraj ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Cellular Therapy ◽  
Refractory Multiple Myeloma

scholarly journals Functional Comparison between Healthy and Multiple Myeloma Adipose Stromal Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Nicolas Espagnolle ◽  
Benjamin Hebraud ◽  
Jean-Gérard Descamps ◽  
Mélanie Gadelorge ◽  
Marie-Véronique Joubert ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stromal Cells ◽  
Cellular Therapy ◽  
Plasma Cells ◽  
Bone Lesions ◽  
Adipose Stromal Cells ◽  
Osteolytic Lesions ◽  
Healthy Donors ◽  
Bone Damage ◽  
First Time

Multiple myeloma (MM) is an incurable B cell neoplasia characterized by the accumulation of tumor plasma cells within the bone marrow (BM). As a consequence, bone osteolytic lesions develop in 80% of patients and remain even after complete disease remission. We and others had demonstrated that BM-derived mesenchymal stromal cells (MSCs) are abnormal in MM and thus cannot be used for autologous treatment to repair bone damage. Adipose stromal cells (ASCs) represent an interesting alternative to MSCs for cellular therapy. Thus, in this study, we wondered whether they could be a good candidate in repairing MM bone lesions. For the first time, we present a transcriptomic, phenotypic, and functional comparison of ASCs from MM patients and healthy donors (HDs) relying on their autologous MSC counterparts. In contrast to MM MSCs, MM ASCs did not exhibit major abnormalities. However, the changes observed in MM ASCs and the supportive property of ASCs on MM cells question their putative and safety uses at an autologous or allogenic level.

scholarly journals Measles Reactivity in Windsor Patients Post Autologous Versus Allogeneic Hematopoietic Cell Transplantation: A Retrospective Review

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 30-30
Author(s):  
Kayla Negus ◽  
Mohammad Jarrar ◽  
Indryas L. Woldie ◽  
Sindu M. Kanjeekal ◽  
Kit McCann ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Hematopoietic Cell Transplantation ◽  
Cellular Therapy ◽  
Immune Status ◽  
The United States ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Post Transplant ◽  
Allogeneic Hct ◽  
Autologous Hct

Background As the antivaccine movement has increased, vaccine preventable illnesses have also increased. The resurgence of measles globally has been noted, specifically the United States received 1200 new cases of measles in 2019, which is the highest number of cases since 1994. Measles is a highly contagious pathogen; the virus has an attack rate of up to 90% in susceptible individuals. Standard of care for patients post hematopoietic cell transplant (HCT) includes repeating all childhood vaccinations. However, compliance with recommendations is unknown. No previous reports have been created measuring the difference in measles, mumps, and rubella (MMR) reactivity between autologous and allogeneic HCT patients post treatment. Methods A retrospective chart review investigated HCT patients between 2000-2019 from the Windsor Regional Hospital (WRH) cancer centre. Patients were excluded from data collection if they were deceased before an MMR reactivity test could be done or if they were lost to follow up. A total of 83% of autologous HCT (N=57) and 66% of allogeneic HCT (N=47) patients had serology tested to measure MMR reactivity post-transplant prior to live vaccinations. MMR titres were drawn from autologous patients a median of 395 days after HCT and a median of 907 days after HCT for allogeneic patients. Results Overall, allogeneic HCT patients had more reactivity than autologous HCT patients as seen in Table 1. Conclusion All patients not reactive to measles need to be re-vaccinated 24 months after treatment according to 2019 American Society for Transplantation and Cellular Therapy guidelines. Our patients are treated in a variety of transplant centers in Ontario, Canada as well as Detroit, Michigan; which is of concern because measles cases have been reported in Detroit. The majority (66%) of allogeneic HCT patients had a myeloid malignancy, while 70% of autologous patients has a diagnosis of multiple myeloma. As evidenced by the poor MMR response, less robust immune systems may be accounted for by multiple myeloma patients. This does emphasize the need for MMR vaccinations post HCT for multiple myeloma patients and raises the question regarding immunization for at risk non-transplant eligible patients. We suggest that it may be reasonable to assess MMR immune status in all myeloma patients to determine if this is a transplant effect or an effect of the underlying immune status of the myeloma patient. This study does emphasize the need to assess MMR status post transplant in all myeloma patients, as the vast majority in our study did not demonstrate immunity post stem cell transplant. Figure Disclosures Hamm: Amgen: Consultancy.

Exploring NKG2D and BCMA-CAR NK-92 for Adoptive Cellular Therapy to Multiple Myeloma

2019 ◽  
Vol 19 (10) ◽  
pp. e24-e25 ◽  
Author(s):  
Elena Maroto Martín ◽  
Jessica Encinas ◽  
Almudena García-Ortiz ◽  
Laura Ugalde ◽  
Rafael Alonso Fernández ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cellular Therapy ◽  
Adoptive Cellular Therapy

scholarly journals Rapid Progress in Immunotherapies for Multiple Myeloma: An Updated Comprehensive Review

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2712
Author(s):  
Hiroko Nishida
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Cellular Therapy ◽  
Nk Cell ◽  
Checkpoint Inhibitors ◽  
Unmet Need ◽  
Durable Response ◽  
Comprehensive Review ◽  
Dc Vaccine ◽  
Car T

Despite rapid advances in treatment approaches of multiple myeloma (MM) over the last two decades via proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies (mAbs), their efficacies are limited. MM still remains incurable, and the majority of patients shortly relapse and eventually become refractory to existing therapies due to the genetic heterogeneity and clonal evolution. Therefore, the development of novel therapeutic strategies with different mechanisms of action represents an unmet need to achieve a deep and highly durable response as well as to improve patient outcomes. The antibody-drug conjugate (ADC), belanatmab mafadotin, which targets B cell membrane antigen (BCMA) on plasma cells, was approved for the treatment of MM in 2020. To date, numerous immunotherapies, including bispecific antibodies, such as bispecific T cell engager (BiTE), the duobody adoptive cellular therapy using a dendritic cell (DC) vaccine, autologous chimeric antigen (CAR)-T cells, allogeneic CAR-natural killer (NK) cells, and checkpoint inhibitors have been developed for the treatment of MM, and a variety of clinical trials are currently underway or are expected to be planned. In the future, the efficacy of combination approaches, as well as allogenic CAR-T or NK cell therapy, will be examined, and promising results may alter the treatment paradigm of MM. This is a comprehensive review with an update on the most recent clinical and preclinical advances with a focus on results from clinical trials in progress with BCMA-targeted immunotherapies and the development of other novel targets in MM. Future perspectives will also be discussed.

Identification of CS1 Peptides for Induction of Antigen-Specific CTLs in Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1611-1611
Author(s):  
Weihua Song ◽  
Yu-Tzu Tai ◽  
Tetsuro Sasada ◽  
Peter Burger ◽  
Mariateresa Fulciniti ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Lymphocytes ◽  
Immune Responses ◽  
Cellular Therapy ◽  
Surface Glycoprotein ◽  
Target Cells ◽  
Cell Surface Glycoprotein ◽  
Specific Ctls ◽  
High Binding

Abstract Despite progress in the treatment of multiple myeloma (MM), the disease remains incurable. Therefore novel therapeutic approaches are required to achieve better outcome in patients. Development of peptide-based immunotherapy against tumor specific or associated antigens offers an attractive approach that may lead to tumor-targeted cellular therapy in MM patients. Recently, CS1 (CD2 subset 1, CRACC, SLAMF7), a cell surface glycoprotein of the CD2 family, was found to be highly expressed by the tumor cells of the majority of MM patients but not other normal tissues. Importantly, a novel anti-CS1 HuLuc63 mAb induced significant anti-myeloma killing in vitro and in vivo (Abstract #950059). In addition, CS1 may play a role in MM cell survival (Abstract #953659). In this study, we asked whether CS1 is a suitable myeloma-associated antigen for cellular therapy in MM. We wanted to identify potential immunogenic peptides derived from CS1 and tested whether these peptides evoke MM-specific cytotoxic T lymphocytes (CTLs). First, we predicted the potential peptide sequences of CS1 that could bind to HLA-A*0201 molecule using three databases (RANKPEP, BIMAS and NetMHC). A total of four peptides were selected and synthesized according to the high binding scores among all the databases. Next, peptide-T2 cells binding assay confirmed these peptides with high binding affinity to HLA-A*0201 molecule (Fluorescence index: 2.19, 3.28, 3.44 and 3.49). To generate the peptide-specific CTLs, HLA-A*0201-positive normal human CD8+ T lymphocytes were stimulated with autologuous dendritic cells (DCs) or T2 cells pulsed with candidate CS1-peptides. The CTL cell lines were established after several rounds restimulation. We have evaluated the immunogenicity of the expanded CTLs by the stimulation with peptide-pulsed or unpulsed T2 cells. Our data demonstrated that one peptide-induced CTLs (CS1-CTLs) possessed high antigen-specific immune responses with the HLA-A*0201-restriction relative to a certain level of immune responses displayed by another three peptide-induced CTLs. We further evaluated the proliferative activity of CS1-CTLs by 3H-TdR incorporation assay. Upon stimulation by peptide-pulsed T2 cells, the cell proliferation of CS1-specific CTLs increased approximately 55-fold, compared with unstimulated cells (pulsed vs. unpulsed: 22894 vs. 423 cpm). The activation of CS1-CTLs was monitored by the expression of CD25 (IL-2Rα chain) on peptide-stimulated CS1-CTLs (%CD25+ cells: pulsed vs. unpulsed: 98% vs. 13%). CS1-CTLs significantly secreted 14-fold higher levels of IFN- γ in response to peptide-pulsed T2 cells (pulsed vs. unpulsed: 615 vs. 46 pg/ml). Importantly, the expanded CS1-CTLs generated high cytotoxicity (93%) in response to peptide pulsed T2 cells. Furthermore, more than 30% of killing activity by CS1-CTLs against HLA-A*0201+CS1+ MCCAR cells was observed at the effector: target ratio of 20:1. In contrast, these CS1-CLTs did not kill HLA-A*0201+/CS1− U266 and HLA-A*0201−/CS1+ MM1S target cells. These results support CS1 as an antigenic target for the induction of peptide-specific CTLs against MM cells. Further functional studies are underway to confirm potential CS1-specific cellular therapy to treat MM.

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