Cancer remains a major public health problem. With 1 in 6 deaths attributed to cancer, the disease is the second leading cause of death in the United States and around the world. In 2020, it is estimated that 9.6 million died of the disease.[1]

The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted. This progress is driven by long-term declines in death rates for the 4 leading cancers (lung, colorectal, breast, prostate).[1]

The mainstays of cancer therapy, including radiation therapy, surgery, and systemic chemotherapy, are limited in efficacy.

Antibody-based Therapeutics
Following the development of the hybridoma technique by Köhler and Milstein in 1975, which made it possible to obtain pure antibodies in large amounts, greatly enhanced basic research and development of novel therapeutic agents. [2]

In the years since then, additional scientific and technological advances have made the translation of therapeutic antibodies possible. One reason for the considerable success and clinical benefit of antibody-based anti-cancer therapeutics is that they have increasingly fewer adverse effects due to their high specificity.  This, in turn, has made these agents a predominant class of new drugs developed and approved in recent years.  Among these targeted agents are Antibody-drug Conjugates or ADC, a class of highly targeted, anti-cancer drugs.

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Antibody-drug conjugates
Being a complex and evolving class of agents specifically designed with the objective of delivering anti-cancer agents in the most precise and selectively targeted way to cancer cells, they are composed of four key components – a target antigen, an antibody construct, a cytotoxic payload, and a chemical linker moiety that couples the payload with the antibody.[3]

A better understanding of cancer biology, better antibody selection platforms, and improved antibody conjugation methodologies to create novel ADC constructs, has led to the approval of 10 ADCs by the Food and Drug Administration (FDA), one ADC being approved by the Chinese regulator and one biosimilar ADC.

And while the development of ADC today is still focusing on oncology and hematology, researchers, driven by the identification of novel targets and advances in linker/payload technologies, are developing novel agents designed to treat inflammation, diabetes, and many other diseases and disorders.

For example, one group of investigators is developing conditioning agents designed to ‘reset’ the immune system to halt disease progression in multiple models of sclerosis, systemic sclerosis, and inflammatory arthritis and create a targeted, disease-modifying antibody-drug conjugate designed to selectively and rapidly remove disease-causing cells in the body and enable an immune and blood system reset and long-term engraftment, without the need for aggressive chemotherapy or radiation. [3][4]

Sutro Biopharma
In a recent episode of The Onco’Zine Brief Peter Hofland, Ph.D. spoke with William (Bill) Newell, JD, Chief Executive Officer and a member of the Board of Directors of Sutro Biopharma.

Sutro is a clinical-stage drug discovery, development, and manufacturing company using precise protein engineering and rational design to advance the development of the next-generation oncology therapeutics for unmet medical needs and areas where the current standard of care is suboptimal.

The company’s scalable biochemical cell-free protein synthesis technology platform XpressCF®, the company’s non-natural amino acid conjugation technology XpressCF+™ and the company’s discovery technology ProteinSAR™, have led to the development of cytokine-based immuno-oncology therapies, antibody-drug conjugates or ADCs, vaccines, and bispecific antibodies.

In addition to Sutro’s own pipeline of novel drugs, including STRO-001, a CD74-targeting ADC currently being investigated in a Phase 1 clinical trial of patients with advanced B-cell malignancies, such as multiple myeloma and non-Hodgkin lymphoma, and STRO-002, a folate receptor alpha (FolRα)-targeting ADC, currently being investigated in a Phase 1 clinical trial of patients with ovarian and endometrial cancers, the company is also collaborating with select pharmaceutical and biotech companies to discover and develop novel, next-generation therapeutics.

In the broadcast, Hofland and Newell talk about ADCs in general, about Sutro and the company’s proprietary platform technology, products, and partners, and about developments in the industry confirming that antibody-drug conjugates are, indeed, coming of age.

The program is available via Spreaker, UK Health Radio, PRX | Public Radio Exchange, iHeart Radio, Spotify, iTunes, and most podcast platforms.

Reference
[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590. Epub 2020 Jan 8. PMID: 31912902.
[2] Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495-7. doi: 10.1038/256495a0. PMID: 1172191.
[3] What are Antibody-drug Conjugates? The Review. Online. ADC Review | Journal of Antibody-drug Conjugates. Online. Last accessed on June 23, 2021
[4] Immune System Reset May Halt Multiple Sclerosis Progression. NIH Research Matters; National Institute of Health. Online. Last accessed on June 23, 2021.
[5] Gingrich J.How the Next Generation Antibody Drug Conjugates Expands Beyond Cytotoxic Payloads for Cancer Therapy. Online. ADC Review | Journal of Antibody-drug Conjugates. Online. Last accessed on June 23, 2021

Featured Image: STRO-002 is a folate receptor alpha (FolRα)-targeting ADC, currently being investigated in a Phase 1 clinical trial of patients with ovarian and endometrial cancers. The drug is being developed by Sutro BioPharma using the company’s proprietary and integrated cell-free protein synthesis platform XpressCF® and site-specific conjugation platform XpressCF+™. Courtesy: © 2016 – 2021 Sutro BioPharma. Used with permission.

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