Antibody-drug conjugates in clinical trials for lymphoid malignancies and multiple myeloma

Yu, Bo; Liu, Delong

doi:10.1186/s13045-019-0786-6

Cited by 79 publications

(97 citation statements)

References 154 publications

(165 reference statements)

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“…A special category of these antigens comprises neoantigens, which are present on MHC molecules (38,39) (Figure 1). Surprisingly, neoantigens are unique to the patient rather than to the tumor, and are often downregulated in tumors, suggesting that tumors evade immune destruction (40)(41)(42)(43)(44)(45). These properties make neoantigens suitable targets for personalizing cancer vaccines and ACT (46,47).…”

Section: Tumor Immunosurveillance and Tumor Antigensmentioning

confidence: 99%

“…Targeted antibodies are antibodies customized to recognize specific cancer cell antigens. In addition to the use of cancer-specific monoclonal antibodies (mAb), two potent customizations, namely antibody-drug conjugates (ADCs), and bi-specific T cell-engaging antibodies (BiTEs) are being tested as anti-cancer immunotherapies, several of which have been approved primarily for hematological malignancies (45,47). ADCs are highly potent constructs of tumor-specific mAbs equipped with anti-cancer drugs which are effective once internalized by a tumor cell (45).…”

Section: Targeted Antibodiesmentioning

confidence: 99%

“…In addition to the use of cancer-specific monoclonal antibodies (mAb), two potent customizations, namely antibody-drug conjugates (ADCs), and bi-specific T cell-engaging antibodies (BiTEs) are being tested as anti-cancer immunotherapies, several of which have been approved primarily for hematological malignancies (45,47). ADCs are highly potent constructs of tumor-specific mAbs equipped with anti-cancer drugs which are effective once internalized by a tumor cell (45). BiTEs provide enhanced efficacy and safety by simultaneously binding a cancer cell antigen and the CD3 of T cells, thereby directing the host immunity toward a T cell-driven cytotoxic antitumor immune response (47).…”

Section: Targeted Antibodiesmentioning

confidence: 99%

See 2 more Smart Citations

Insights Into Lung Cancer Immune-Based Biology, Prevention, and Treatment

et al. 2020

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Section: Tumor Immunosurveillance and Tumor Antigensmentioning

confidence: 99%

Section: Targeted Antibodiesmentioning

confidence: 99%

Section: Targeted Antibodiesmentioning

confidence: 99%

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Insights Into Lung Cancer Immune-Based Biology, Prevention, and Treatment

et al. 2020

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“…In addition, anti-CD22 ADCs inotuzumab-ozogamicin and moxetumomab-pasudotox were granted approval for patients with R/R B-cell acute lymphoblastic leukemia (2017), and R/R hairy cell leukemia (2018), respectively [26,27]. Several ADCs, e.g., anti-CD19 and anti-CD37, are currently in various stages of clinical development [28].…”

Section: Antibody-drug Conjugates and Targeted-drug Deliverymentioning

confidence: 99%

Drug Resistance in Non-Hodgkin Lymphomas

Klener

Klánová

2020

IJMS

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Non-Hodgkin lymphomas (NHL) are lymphoid tumors that arise by a complex process of malignant transformation of mature lymphocytes during various stages of differentiation. The WHO classification of NHL recognizes more than 90 nosological units with peculiar pathophysiology and prognosis. Since the end of the 20th century, our increasing knowledge of the molecular biology of lymphoma subtypes led to the identification of novel druggable targets and subsequent testing and clinical approval of novel anti-lymphoma agents, which translated into significant improvement of patients’ outcome. Despite immense progress, our effort to control or even eradicate malignant lymphoma clones has been frequently hampered by the development of drug resistance with ensuing unmet medical need to cope with relapsed or treatment-refractory disease. A better understanding of the molecular mechanisms that underlie inherent or acquired drug resistance might lead to the design of more effective front-line treatment algorithms based on reliable predictive markers or personalized salvage therapy, tailored to overcome resistant clones, by targeting weak spots of lymphoma cells resistant to previous line(s) of therapy. This review focuses on the history and recent advances in our understanding of molecular mechanisms of resistance to genotoxic and targeted agents used in clinical practice for the therapy of NHL.

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“…New advances in the design and manufacture of MoAbs, Bispecific T cell engagers (BiTEs), and antibody-drug conjugates (ADCs) make the antibody-directed agents more powerful with less toxicities [1,[10][11][12]. Blinatumomab as the first approved CD19-targeted BiTE is being studied for induction therapy for elderly patients with acute lymphoblastic leukemia (ALL) and for incorporation into the regimens containing the CD22-targeted ADC, inotuzumab ozogamicin, in an attempt to enhance efficacy and reduce toxicities [13][14][15]. ADCs targeting CD30, CD33, or CD79 have been approved for clinical therapy of lymphomas and AML with the appropriate targets [16][17][18].…”

Section: Antibodies: More On-target and Less Off-tumor Effectsmentioning

confidence: 99%

CAR-T “the living drugs”, immune checkpoint inhibitors, and precision medicine: a new era of cancer therapy

Liu

2019

J Hematol Oncol

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New advances in the design and manufacture of monoclonal antibodies, bispecific T cell engagers, and antibodydrug conjugates make the antibody-directed agents more powerful with less toxicities. Small molecule inhibitors are routinely used now as oral targeted agents for multiple cancers. The discoveries of PD1 and PD-L1 as negative immune checkpoints for T cells have led to the revolution of modern cancer immunotherapy. Multiple agents targeting PD1, PD-L1, or CTLA-4 are widely applied as immune checkpoint inhibitors (ICIs) which alleviate the suppression of immune regulatory machineries and lead to immunoablation of once highly refractory cancers such as stage IV lung cancer. Tisagenlecleucel and axicabtagene ciloleucel are the two approved CD19-targeted chimeric antigen receptor (CAR) T cell products. Several CART cell platforms targeting B cell maturation antigen (BCMA) are under active clinical trials for refractory and/or relapsed multiple myeloma. Still more targets such as CLL-1, EGFR, NKG2D and mesothelin are being directed in CART cell trials for leukemia and solid tumors. Increasing numbers of novel agents are being studied to target cancer-intrinsic oncogenic pathways as well as immune checkpoints. One such an example is targeting CD47 on macrophages which represents a "do-not-eat-me" immune checkpoint. Fueling the current excitement of cancer medicine includes also TCR-T cells, TCR-like antibodies, cancer vaccines and oncolytic viruses.

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Antibody-drug conjugates in clinical trials for lymphoid malignancies and multiple myeloma

Cited by 79 publications

References 154 publications

Insights Into Lung Cancer Immune-Based Biology, Prevention, and Treatment

Insights Into Lung Cancer Immune-Based Biology, Prevention, and Treatment

Drug Resistance in Non-Hodgkin Lymphomas

CAR-T “the living drugs”, immune checkpoint inhibitors, and precision medicine: a new era of cancer therapy

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