An important class of cancer drugs – Antibody Drug Conjugates (ADCs)

The antibody drug conjugates are a new class of drugs in the filed of Cancer Medicine. They are also called as ADCs. It is an antibody which is targeted to Cancer cells. The antibodies are piggy back with a linker to potent chemotherapy drug. Therefore it seems to act as a targeted missile carrying the war head with the capacity to kill the Cancer cells. By achieving this targeted delivery, antibody drug conjugates are able to minimize the collateral damage or side effects to the normal healthy cells of the body.

The field of ADCs is evolving very rapidly and there are many types in trials and approved ADCs for the current use in multiple cancers. According to a paper published in Nature, the first ADC, Mylotarg (gemtuzumab ozogamicin), was approved in 2000 by the US Food and Drug Administration (FDA).

https://www.nature.com/articles/s41392-022-00947-7

The ADCs are novel anti-cancer drugs that are also known as “biological missiles”, which potentially are leading a new era of targeted cancer therapy. There is no doubt that the list of the ADCs is getting larger with time; for example, the Enhertu is approved in Breast Cancer, HER2 mutant Lung Cancer, Gastric Cancer and Gastroesophageal adenocarcinoma (esophageal cancer).

The U.S. Food and Drug Administration in August 2022, approved Enhertu (fam-trastuzumab-deruxtecan-nxki), an IV infusion for the treatment of patients with unresectable (unable to be removed) or metastatic (spread to other parts of the body) HER2-low breast cancer. There are multiple ADCs that are being studied or approved in different cancer subtypes.

Breast Cancer:

• Ado-trastuzumab emtansine (Kadcyla) in HER2 positive breast cancer (adjuvant or metastatic)
• Enhertu (fam-trastuzumab-deruxtecan-nxki) in HER2 expressing breast cancer
• TRODELVY (sacituzumab govitecan-hziy) in triple negative metastatic breast cancer.

Lung Cancer:

• Enhertu (fam-trastuzumab-deruxtecan-nxki) in HER2 mutant metastatic disease

Gastric Cancer/Gastroesophageal Cancer:

• Enhertu (fam-trastuzumab-deruxtecan-nxki)

Bladder Cancer:

• PADCEV (enfortumab vedotin-ejfv)a Nectin-4-directed antibody and microtubule inhibitor conjugate
• TRODELVY (sacituzumab govitecan-hziy)

Multiple Myeloma:

• Belantamab mafodotin–blmf (Blenrep) first-in-class antibody-drug conjugate directed against B-cell maturation antigen (BCMA)

Hodgkin Lymphoma:

• ADCETRIS (brentuximab vedotin), an antibody drug conjugate (ADC) targets CD30-expressing cancer cells.

Diffuse Large B-cell Lymphoma (DLBCL):

• POLIVY (polatuzumab vedotin-piiq) targets CD79b
• MONJUVI (tafasitamab-cxix) in combination with Lenalidomide
• ZYNLONTA® (loncastuximab tesirine-lpyl)

Acute Myeloid Leukemia (AML):

• MYLOTARG (gemtuzumab ozogamicin) targets CD33-positive newly diagnoses and relapsed/refractory acute myeloid leukemia

Acute Lymphoblastic Leukemia (ALL):

• BESPONSA (inotuzumab ozogamicin) for relapsed or refractory B-cell precursor acute lymphoblastic leukemia 

Hairy Cell Leukemia:

• Moxetumomab pasudotox-tdfk (LUMOXITI), a CD22-directed for adult patients with relapsed or refractory hairy cell leukemia (HCL)

Cervical Cancer: 

• Tisotumab vedotin-tftv (Tivdak), a tissue factor-directed antibody and microtubule inhibitor conjugate, for patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

The ADCs have created a new era of hope after its decades of research and endless efforts, however, they also come with side effects which should always be discussed with a treating physician. The future with ADCs will bring more options and play significant role in the changing treatment landscape of cancer.