Dr. Raajit Chanana
Anti Body Drug Conjugate (ADC): Role in Managing Advanced Cancers
Jun 19, 2024
2 Minutes Read
Oncology Blogs
Being one of the spine-chilling diseases in the world, cancer took around 10 million lives around the globe in 2023. These numbers are high for several reasons, delay in diagnoses , Metastatic presentation limited treatment options, etc.
Though there are several cancer treatment therapies, such as chemotherapy, Radiotherapy and hormone therapy. Each has its own advantage and disadvantages including toxicities ,like Alopecia ( Hair Fall ) , Drop in Blood Parameteres
ADC, or antibody-drug conjugate, is a new state-of-the-art solution that surpasses conventional methods for treating advanced cancers. So now, what is it, and how can it help? Let’s read ahead and find out!
What is an Anti-Body Drug Conjugate?
Also can be understood as a Guided Missile , These specialized therapeutic agents represent a convergence of precise targeting, potent cytotoxicity, and reduced systemic toxicity, offering renewed hope for tackling challenging diseases like cancer..
At their core, ADCs consist of three key components:
Monoclonal Antibody (mAb): This serves as the guiding element of the ADC, selectively binding to specific antigens that are overexpressed on the surface of cancer cells. The antibody component ensures targeted delivery of the therapeutic payload to the tumor site.
Linker: Acting as a bridge between the antibody and the cytotoxic drug, the linker is crucial for maintaining stability during circulation in the bloodstream and releasing the payload only when the ADC reaches its target within the cancer cell.
Cytotoxic Payload: This is the potent drug component of the ADC, typically a highly toxic agent such as a chemotherapeutic drug or a cytotoxin. Once released inside the cancer cell, the payload
The First ADC Approved was in MAY 2020 for Blood Malignancy : AML ( Acute Myeloid Leukaemia )
How Does An Antibody Drug Conjugate Help in Managing Cancers?
The ADC is like a targeted biological missile that targets and destroys cancer cells. Its overall mechanism is simple!
The mAb is introduced to the cancer cells, directly binding to the targeted antigens. Further, the cells endocytose the released ADC while forming an early endosome.
The maturation of the early endosome happens, after which the ADC fuses with the lysosomes.
This is the primary part of the process. Once the ADC fuses with the lysosomes, the Cytotoxic Drug or killer payload is injected into the lysosomes. This is done either by chemical or enzyme mediation.
The injection of the Cytotoxic Payload results in DNA and microtubule targeting, which directly enables the process of cell apoptosis, where the cancer cells die.
Based on the permeability of the Cytotoxic drug, the bystander effect is established where the tumour's microenvironment is altered. This directly boosts the efficacy and killing effect of the ADC. This is the whole mechanism of the working of the Antibody Drug Conjugate.
Benefits of Antibody Drug Conjugate
The use of ADC for cancer treatment has several benefits. Here are some of the primary ones.
Targeted Therapy -The Antibody Drug Conjugate is a magic bullet that provides targeted treatment to the cancer cells. By releasing the Cytotoxic payload to the specific tumour-associated antigen, the ADC can kill the cancer cells without affecting the healthy cells around it.
Enhanced Effectiveness- Better targeting of the ADC in treating cancer can help increase efficiency. As the drug requirement for the treatment is low, the delivery of it significantly reduces the chances of any side effects. .
Management of Multitudes of Cancers
According to current research, Antibody Drug Conjugates (ADCs) are used to treat several types of cancer, including breast, ovarian, blood malignancies and lung cancer. Several types of ADCs are revolutionising the treatment of breast cancer.
Side-Effects of Antibody Drug Conjugate
Some adverse effects of Antibody Drug Conjugates can depend on the protein they are made to target. Moreover, the type of cytotoxic drug used in ADC also matters.
If the cytotoxic drug is too toxic and is released into the blood earlier than it reaches the cancer cells, it may lead to several adverse effects, such as
Low red and white cell count
Nerve pain
Low platelet count
Damage to liver
Changes in vision
What are the various anti-body drug conjugations used for cancer treatment?
Some of the FDA-approved ADCs that are used for the treatment of breast and blood cancers are
Brentuximab vedotin - Fit for Hodgkin lymphoma
Polatuzumab vedotin-piiq - Fit for relapsed diffuse large B-cell lymphoma
Gemtuzumab ozogamicin - Fit for relapsed acute myeloid leukaemia
Inotuzumab ozogamicin - Ideal for relapsed B-cell precursor acute lymphoblastic leukaemia
- Enhertu (Fam-trastuzumab-deruxtecan-nxki) –For Metastatic Her2Neu Expressor Breast Cancer
Conclusion
Antibody Drug Conjugates (ADCs) are a novel, highly targeted, and highly effective cancer treatment. As listed, several types of ADCs are available, and many others are being tested and have yet to be approved by the FDA. Contacting a healthcare professional can help you access the right ADC for cancer treatment.
ADC have shown remarkable efficacy in cases where traditional therapies may have faltered, offering renewed hope for patients with limited treatment options.
Looking ahead, the future of ADCs holds immense promise with ongoing advancements in antibody engineering, linker chemistry, and drug development. As researchers delve deeper into understanding tumor biology and refining targeting strategies, the potential applications of ADCs are poised to expand, potentially transforming the treatment landscape for many cancers.
Frequently Asked Questions About Antibody Drug Conjugate
Q. What are ADCs in cancer treatment?
A. ADCs are modern-day pharmacological compounds that can treat several cancers with absolute effectiveness and targeting. Because they target only the specific cancer cells, they induce less toxicity and fewer side effects.
Q. What is the mechanism of action of ADCs?
A. The chemical linker in the ADC process promotes the release of the payload or cytotoxic drug, which ultimately helps in cancer cell DNA damage.
Q. What are the components of ADCs?
A. An ADC has three primary components: a monoclonal antibody, a cytotoxic payload, and a chemical linker.
Q. What are the various ADCs?
A. There are many ADCs approved by the FDA( 13 as on May 2024 ) , including Brentuximab vedotin, Polatuzumab vedotin-piiq, Gemtuzumab ozogamicin, and Inotuzumab ozogamicin., TDM1 , T-DxD ( Enhertu )
Q. Are there any negative effects of ADCs?
A. If the ADC is released into the blood before it reaches the cancer cells, there can be issues such as blood cell and platelet depletion.
References:
- https://www.nature.com/articles/s41392-022-00947-7
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10475555/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10475555/
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