CD38: A Target for Immunotherapeutic Approaches in Multiple Myeloma

Fabio Morandi, Alberto L Horenstein, Federica Costa, Nicola Giuliani, Vito Pistoia, Fabio Malavasi

Research output: Contribution to journalReview article

Abstract

Multiple Myeloma (MM) is a hematological cancer characterized by proliferation of malignant plasma cells in the bone marrow (BM). MM represents the second most frequent hematological malignancy, accounting 1% of all cancer and 13% of hematological tumors, with ~9,000 new cases per year. Patients with monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic smoldering MM (SMM) usually evolve to active MM in the presence of increased tumor burden, symptoms and organ damage. Despite the role of high dose chemotherapy in combination with autologous stem cell transplantation and the introduction of new treatments, the prognosis of MM patients is still poor, and novel therapeutic approaches have been tested in the last years, including new immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies (mAbs). CD38 is a glycoprotein with ectoenzymatic functions, which is expressed on plasma cells and other lymphoid and myeloid cell populations. Since its expression is very high and uniform on myeloma cells, CD38 is a good target for novel therapeutic strategies. Among them, immunotherapy represents a promising approach. Here, we summarized recent findings regarding CD38-targeted immunotherapy of MM in pre-clinical models and clinical trials, including (i) mAbs (daratumumab and isatuximab), (ii) radioimmunotherapy, and (iii) adoptive cell therapy, using chimeric antigen receptor (CAR)-transfected T cells specific for CD38. Finally, we discussed the efficacy and possible limitations of these therapeutic approaches for MM patients.

Original languageEnglish
Pages (from-to)2722
Number of pages9
JournalFrontiers in Immunology
Volume9
DOIs
Publication statusPublished - 2018

Fingerprint

Multiple Myeloma
Plasma Cells
Immunotherapy
Monoclonal Antibodies
Monoclonal Gammopathy of Undetermined Significance
Radioimmunotherapy
Neoplasms
Proteasome Inhibitors
Stem Cell Transplantation
Hematologic Neoplasms
Myeloid Cells
Therapeutics
Cell- and Tissue-Based Therapy
T-Cell Antigen Receptor
Combination Drug Therapy
Tumor Burden
Glycoproteins
Bone Marrow
Clinical Trials
Lymphocytes

Cite this

CD38 : A Target for Immunotherapeutic Approaches in Multiple Myeloma. / Morandi, Fabio; Horenstein, Alberto L; Costa, Federica; Giuliani, Nicola; Pistoia, Vito; Malavasi, Fabio.

In: Frontiers in Immunology, Vol. 9, 2018, p. 2722.

Research output: Contribution to journalReview article

Morandi, Fabio ; Horenstein, Alberto L ; Costa, Federica ; Giuliani, Nicola ; Pistoia, Vito ; Malavasi, Fabio. / CD38 : A Target for Immunotherapeutic Approaches in Multiple Myeloma. In: Frontiers in Immunology. 2018 ; Vol. 9. pp. 2722.
@article{a77c4a92ec774d9fb2fd7a21bd890c74,
title = "CD38: A Target for Immunotherapeutic Approaches in Multiple Myeloma",
abstract = "Multiple Myeloma (MM) is a hematological cancer characterized by proliferation of malignant plasma cells in the bone marrow (BM). MM represents the second most frequent hematological malignancy, accounting 1{\%} of all cancer and 13{\%} of hematological tumors, with ~9,000 new cases per year. Patients with monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic smoldering MM (SMM) usually evolve to active MM in the presence of increased tumor burden, symptoms and organ damage. Despite the role of high dose chemotherapy in combination with autologous stem cell transplantation and the introduction of new treatments, the prognosis of MM patients is still poor, and novel therapeutic approaches have been tested in the last years, including new immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies (mAbs). CD38 is a glycoprotein with ectoenzymatic functions, which is expressed on plasma cells and other lymphoid and myeloid cell populations. Since its expression is very high and uniform on myeloma cells, CD38 is a good target for novel therapeutic strategies. Among them, immunotherapy represents a promising approach. Here, we summarized recent findings regarding CD38-targeted immunotherapy of MM in pre-clinical models and clinical trials, including (i) mAbs (daratumumab and isatuximab), (ii) radioimmunotherapy, and (iii) adoptive cell therapy, using chimeric antigen receptor (CAR)-transfected T cells specific for CD38. Finally, we discussed the efficacy and possible limitations of these therapeutic approaches for MM patients.",
author = "Fabio Morandi and Horenstein, {Alberto L} and Federica Costa and Nicola Giuliani and Vito Pistoia and Fabio Malavasi",
year = "2018",
doi = "10.3389/fimmu.2018.02722",
language = "English",
volume = "9",
pages = "2722",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S.A.",

}

TY - JOUR

T1 - CD38

T2 - A Target for Immunotherapeutic Approaches in Multiple Myeloma

AU - Morandi, Fabio

AU - Horenstein, Alberto L

AU - Costa, Federica

AU - Giuliani, Nicola

AU - Pistoia, Vito

AU - Malavasi, Fabio

PY - 2018

Y1 - 2018

N2 - Multiple Myeloma (MM) is a hematological cancer characterized by proliferation of malignant plasma cells in the bone marrow (BM). MM represents the second most frequent hematological malignancy, accounting 1% of all cancer and 13% of hematological tumors, with ~9,000 new cases per year. Patients with monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic smoldering MM (SMM) usually evolve to active MM in the presence of increased tumor burden, symptoms and organ damage. Despite the role of high dose chemotherapy in combination with autologous stem cell transplantation and the introduction of new treatments, the prognosis of MM patients is still poor, and novel therapeutic approaches have been tested in the last years, including new immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies (mAbs). CD38 is a glycoprotein with ectoenzymatic functions, which is expressed on plasma cells and other lymphoid and myeloid cell populations. Since its expression is very high and uniform on myeloma cells, CD38 is a good target for novel therapeutic strategies. Among them, immunotherapy represents a promising approach. Here, we summarized recent findings regarding CD38-targeted immunotherapy of MM in pre-clinical models and clinical trials, including (i) mAbs (daratumumab and isatuximab), (ii) radioimmunotherapy, and (iii) adoptive cell therapy, using chimeric antigen receptor (CAR)-transfected T cells specific for CD38. Finally, we discussed the efficacy and possible limitations of these therapeutic approaches for MM patients.

AB - Multiple Myeloma (MM) is a hematological cancer characterized by proliferation of malignant plasma cells in the bone marrow (BM). MM represents the second most frequent hematological malignancy, accounting 1% of all cancer and 13% of hematological tumors, with ~9,000 new cases per year. Patients with monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic smoldering MM (SMM) usually evolve to active MM in the presence of increased tumor burden, symptoms and organ damage. Despite the role of high dose chemotherapy in combination with autologous stem cell transplantation and the introduction of new treatments, the prognosis of MM patients is still poor, and novel therapeutic approaches have been tested in the last years, including new immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies (mAbs). CD38 is a glycoprotein with ectoenzymatic functions, which is expressed on plasma cells and other lymphoid and myeloid cell populations. Since its expression is very high and uniform on myeloma cells, CD38 is a good target for novel therapeutic strategies. Among them, immunotherapy represents a promising approach. Here, we summarized recent findings regarding CD38-targeted immunotherapy of MM in pre-clinical models and clinical trials, including (i) mAbs (daratumumab and isatuximab), (ii) radioimmunotherapy, and (iii) adoptive cell therapy, using chimeric antigen receptor (CAR)-transfected T cells specific for CD38. Finally, we discussed the efficacy and possible limitations of these therapeutic approaches for MM patients.

U2 - 10.3389/fimmu.2018.02722

DO - 10.3389/fimmu.2018.02722

M3 - Review article

C2 - 30546360

VL - 9

SP - 2722

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

ER -