Antibody–Drug Conjugates as an Emerging Therapy in Oncodermatology

Esnault, Charles; Schrama, David; Houben, Roland; Guyétant, Serge; Desgranges, Audrey; Martin, Camille; Berthon, Patricia; Viaud‐Massuard, Marie‐Claude; Touzé, Antoine; Kervarrec, Thibault; Samimi, Mahtab

doi:10.3390/cancers14030778

Cited by 17 publications

(8 citation statements)

References 129 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prospective melanoma markers already evaluated as ADC targets in the clinic also include the receptor tyrosine kinases ROR2 (NCT03504488) and c-KIT (NCT02221505). 27 In our work, encouraged by the therapeutic efficacy of ADCs targeting alternative markers in tumors known to overexpress ganglioside GD2, we developed conjugates consisting of the ch14.18 antibody—the most prevalent GD2-specific therapeutic in the clinic, a commonly used cleavable linker, and the auristatins MMAE and MMAF that together are employed in almost half of the currently approved drug conjugates. Their cytotoxic activity was evaluated in tumor cell lines of different origin and with different level of GD2 expression, and in two mouse cancer models.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic efficacy of antibody-drug conjugates targeting GD2-positive tumors

Kalinovsky

Kibardin

Холоденко

et al. 2022

J Immunother Cancer

View full text Add to dashboard Cite

BackgroundBoth ganglioside GD2-targeted immunotherapy and antibody-drug conjugates (ADCs) have demonstrated clinical success as solid tumor therapies in recent years, yet no research has been carried out to develop anti-GD2 ADCs against solid tumors. This is the first study to analyze cytotoxic activity of clinically relevant anti-GD2 ADCs in a wide panel of cell lines with varying GD2 expression and their effects in mouse models of GD2-positive solid cancer.MethodsAnti-GD2 ADCs were generated based on the GD2-specific antibody ch14.18 approved for the treatment of neuroblastoma and commonly used drugs monomethyl auristatin E (MMAE) or F (MMAF), conjugated via a cleavable linker by thiol-maleimide chemistry. The antibody was produced in a mammalian expression system, and its specific binding to GD2 was analyzed. Antigen-binding properties and biodistribution of the ADCs in mice were studied in comparison with the parent antibody. Cytotoxic effects of the ADCs were evaluated in a wide panel of GD2-positive and GD2-negative tumor cell lines of neuroblastoma, glioma, sarcoma, melanoma, and breast cancer. Their antitumor effects were studied in the B78-D14 melanoma and EL-4 lymphoma syngeneic mouse models.ResultsThe ch14.18-MMAE and ch14.18-MMAF ADCs retained antigen-binding properties of the parent antibody. Direct dependence of the cytotoxic effect on the level of GD2 expression was observed in cell lines of different origin for both ADCs, with IC50 below 1 nM for the cells with high GD2 expression and no cytotoxic effect for GD2-negative cells. Within the analyzed cell lines, ch14.18-MMAF was more effective in the cells overexpressing GD2, while ch14.18-MMAE had more prominent activity in the cells expressing low GD2 levels. The ADCs had a similar biodistribution profile in the B78-D14 melanoma model compared with the parent antibody, reaching 7.7% ID/g in the tumor at 48 hours postinjection. The average tumor size in groups treated with ch14.18-MMAE or ch14.18-MMAF was 2.6 times and 3.8 times smaller, respectively, compared with the control group. Antitumor effects of the anti-GD2 ADCs were also confirmed in the EL-4 lymphoma model.ConclusionThese findings validate the potential of ADCs targeting ganglioside GD2 in treating multiple GD2-expressing solid tumors.

show abstract

Section: Discussionmentioning

confidence: 99%

Therapeutic efficacy of antibody-drug conjugates targeting GD2-positive tumors

Kalinovsky

Kibardin

Холоденко

et al. 2022

J Immunother Cancer

View full text Add to dashboard Cite

show abstract

“…The cytotoxic drug is released into the cytoplasm and induces apoptosis of the cell via its cytotoxicity. ADCs have historically been used for hematological malignancies (e.g., ADCs targeting CD30, CD79b, CD33, CD22, CD19, and CD38) but have recently been rapidly expanded to solid tumors [ 126 , 127 ]. FDA-approved ADCs for solid tumors include trastuzumab emtansine and trastuzumab deruxtecan (anti-HER2 ADCs) for breast cancer, enfortumab vedotin (anti-NECTIN-4 ADC) for urothelial cancer, sacituzumab govitecan (anti-TROP-2 ADC) for breast cancer, and tisotumab vedotin (anti-tissue factor ADC) for cervical cancer.…”

Section: Treatmentmentioning

confidence: 99%

“…Several melanoma-specific ADCs are currently undergoing preclinical and clinical trials. Reported target antigens are gpNMB, PMEL17, HER3, endothelin B receptor, c-KIT, and anexelekto [ 126 , 136 ]. Although no NAM-specific ADCs have been reported, these antigens are likely to be expressed in NAM.…”

Section: Treatmentmentioning

confidence: 99%

Nail Apparatus Melanoma: Current Management and Future Perspectives

Ito

Hashimoto

Kaku-Ito

et al. 2023

JCM

View full text Add to dashboard Cite

Nail apparatus melanoma (NAM) is a rare type of cutaneous melanoma that belongs to the acral melanoma subtype. NAM is managed principally in accordance with the general treatment for cutaneous melanoma, but there is scarce evidence in support of this in the literature. Acral melanoma is genetically different from non-acral cutaneous melanoma, while recently accumulated data suggest that NAM also has a different genetic background from acral melanoma. In this review, we focus on recent advances in the management of NAM. Localized NAM should be surgically removed; amputation of the digit and digit-preserving surgery have been reported. Sentinel lymph node biopsy can be considered for invasive NAM for the purpose of accurate staging. However, it is yet to be clarified whether patients with metastatic sentinel lymph nodes can be safely spared completion lymph node dissection. Similar to cutaneous melanoma, immune checkpoint inhibitors and BRAF/MEK inhibitors are used as the first-line treatment for metastatic NAM, but data on the efficacy of these therapies remain scarce. The therapeutic effects of immune checkpoint inhibitors could be lower for NAM than for cutaneous melanoma. This review highlights the urgent need to accumulate data to better define the optimal management of this rare melanoma.

show abstract

“…ADCs are the most rapidly emerging monoclonal antibody-based cancer immunotherapy field, with significantly greater potency than naked antibodies [ 242 , 243 ]. This strategy employs a mAb attached to the cytotoxic payload via a chemical linker directed to a target cell surface antigen expressed on the cancer cells [ 244 , 245 , 246 ]. Typically, ADC contains three components: the monoclonal antibody (mAb), the linker, and the cytotoxic or cytostatic/cytotoxic drug.…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Emerging Trends in Immunotherapy for Cancer

et al. 2022

View full text Add to dashboard Cite

Recent advances in cancer immunology have enabled the discovery of promising immunotherapies for various malignancies that have shifted the cancer treatment paradigm. The innovative research and clinical advancements of immunotherapy approaches have prolonged the survival of patients with relapsed or refractory metastatic cancers. Since the U.S. FDA approved the first immune checkpoint inhibitor in 2011, the field of cancer immunotherapy has grown exponentially. Multiple therapeutic approaches or agents to manipulate different aspects of the immune system are currently in development. These include cancer vaccines, adoptive cell therapies (such as CAR-T or NK cell therapy), monoclonal antibodies, cytokine therapies, oncolytic viruses, and inhibitors targeting immune checkpoints that have demonstrated promising clinical efficacy. Multiple immunotherapeutic approaches have been approved for specific cancer treatments, while others are currently in preclinical and clinical trial stages. Given the success of immunotherapy, there has been a tremendous thrust to improve the clinical efficacy of various agents and strategies implemented so far. Here, we present a comprehensive overview of the development and clinical implementation of various immunotherapy approaches currently being used to treat cancer. We also highlight the latest developments, emerging trends, limitations, and future promises of cancer immunotherapy.

show abstract

Antibody–Drug Conjugates as an Emerging Therapy in Oncodermatology

Cited by 17 publications

References 129 publications

Therapeutic efficacy of antibody-drug conjugates targeting GD2-positive tumors

Therapeutic efficacy of antibody-drug conjugates targeting GD2-positive tumors

Nail Apparatus Melanoma: Current Management and Future Perspectives

Emerging Trends in Immunotherapy for Cancer

Contact Info

Product

Resources

About