Biologics Offer a Vast Toolbox for Disease Treatment New

The US Food and Drug Administration (FDA) has approved more than 23,000 prescription drugs, with many more in development. Increasingly, therapeutic manufacturers are discovering that the key to treating disease may have been inside us all along, in the form of biologically-derived treatments called biologics. In this article, explore how researchers use biologics to combat disease.

What Are Biologics?

Biologics are prepared from materials made or expressed in a living system, such as proteins or recombinant DNA technologies from animal cells or microorganisms. As a rapidly expanding class of therapeutics, biologics have transformed the treatment landscape for many conditions. The approach gained traction in the past few decades; the FDA approved the first recombinant biologic, human insulin (Humulin), in 1982.¹ Since then, biologics have evolved significantly in complexity, scope, and therapeutic potential. Currently, clinicians and researchers use biologics to treat illnesses such as cancers, rare genetic diseases, autoimmune disorders such as rheumatoid arthritis, psoriasis, psoriatic arthritis, inflammatory bowel disease, multiple sclerosis, and more.

Biologics often fall into three main categories: those that replace endogenous factors, target and inhibit pathways, or mimic receptors. They differ significantly from traditional pharmacologic agents, which are typically small, chemically synthesized compounds with well-defined structures and predictable functions.² In contrast, biologics are complex molecules produced through a multifaceted process involving cell line selection, cell culture, purification, formulation, production, and rigorous validation.³ Biologics generally have higher molecular weights, less precisely characterized structures, reduced stability, and greater immunogenicity compared to conventional therapies, among other differences.⁴

Biosimilars

Biosimilars are biologic drugs developed to closely resemble an existing approved biologic.⁵ Unlike generics in traditional pharmacotherapy, biosimilars are not identical to their reference products; they have minor differences, typically in their inactive ingredients.

Biosimilars undergo rigorous regulatory approval processes to confirm the same mechanism of action, route of administration, dosage, strength, clinical efficacy, and safety profile as the original biologic. Some biosimilars can earn the special designation of “interchangeable,” allowing pharmacies to substitute them for the reference biologic without a prescribing physician’s approval. To receive this designation, drug companies typically conduct studies in which patients alternate between the reference product and the biosimilar. The outcomes are then compared to those in patients who receive only the reference product. These studies must show that switching does not compromise effectiveness or raise safety concerns. Biosimilars help reduce healthcare costs by lowering development expenses and increasing market competition.⁶

Types of Biologics

Biologics represent a rapidly expanding field of research and innovation, with new types emerging each year. Below is a summary of some of the most well-known biologics and classifications.

1. Peptide Hormones: These are small, biologically active molecules composed of fewer than 100 amino acids. They play essential roles in regulating physiological processes, particularly those related to growth and reproduction. Clinicians have administered one of the earliest therapeutic peptide hormones, insulin, to patients with diabetes since the 1920s, when it was originally extracted from canine and bovine pancreases.⁷ Though insulin is now recognized as a biologic, its use long predates modern regulatory classifications. Since the 1980s, insulin has been produced using recombinant DNA technology. In 2020, the FDA formally reclassified insulin as a biologic, along with other therapeutic hormones such as human growth hormone (somatropin), pancrelipase, and chorionic gonadotropin.⁸

2. Monoclonal and recombinant antibodies: Human plasma cells naturally produce antibodies as part of the immune response to foreign substances and other antigens. In 1975, César Milstein and Georges J. F. Köhler developed the hybridoma technique to generate large quantities of monoclonal antibodies that target specific antigens, a breakthrough that earned them the Nobel Prize in 1984.⁹ Monoclonal antibodies are identical molecules derived from a single B cell clone, meaning they all bind to the same antigen that initially activated that B cell. Several subclasses of biologics are either monoclonal antibodies themselves or partially derived from them. Monoclonal antibodies are perhaps most well-known for their use in treating cancer through mechanisms such as antibody-dependent cellular cytotoxicity, tumor cell signaling inhibition, or T cell activity modulation.¹⁰ However, monoclonal antibodies are also used to treat diseases beyond cancer, particularly autoimmune conditions, by blocking proinflammatory response pathways.

3. Immune checkpoint inhibitors: The human body has built-in off switches to prevent excessive immune activity. Key components of this braking system include immune checkpoint molecules such as CTLA-4, PD-1, and PD-L1. These molecules function as inhibitory signals that attenuate T cell activity to maintain immune homeostasis. Therapeutically blocking this system with monoclonal antibodies enhances immune responses, forming the basis of an increasingly important class of immunotherapies known as immune checkpoint inhibitors (ICIs).¹¹ Currently, all FDA-approved ICIs are for cancer treatment.

4. Chimeric antigen receptor T-cell therapy: A chimeric antigen receptor (CAR) is a synthetic fusion protein designed to specifically recognize target antigens, most commonly those expressed by cancer cells.¹² It consists of four main components: an extracellular binding domain, a hinge region, a transmembrane domain, and one or more intracellular signaling domains.¹³ Once the CAR is engineered, the gene encoding it is introduced into T cells, most often using a viral vector. Researchers incorporate monoclonal antibodies in CAR T-cell therapy design: the extracellular binding domain is derived from the variable heavy and light chains of monoclonal antibodies. CAR T-cell therapies are currently only used to treat hematologic malignancies.

5. Cytokine therapy: Cytokines are small proteins that are essential for signal transduction in various cellular processes, particularly within the immune system. They play key roles in immune regulation and are major contributors to autoimmunity.¹⁴ Notable cytokines include interleukins, interferons, tumor necrosis factor (TNF) superfamily molecules, and chemokines. TNF and interleukin-1 are common targets for cytokine-based therapies. These therapies typically involve decoy receptors or antibodies that target either the cytokines themselves or their receptors. While many cytokine inhibitors are monoclonal antibodies, some, such as etanercept, are fusion proteins. Cytokine therapies are widely used to treat autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, and ankylosing spondylitis, among others. A smaller number of cytokine inhibitors have been approved for the treatment of cancer, and research in this field is ongoing.¹⁵

6. Anti-tumor vaccines: Cancer vaccines can be either preventive or therapeutic. Although specific methods vary, at their core, anti-tumor vaccines work by priming the immune system to recognize and attack cancer-specific antigens.¹⁶ These antigens may be shared, meaning commonly expressed across multiple cancer types, or personalized neoantigens uniquely expressed by an individual tumor. Perhaps the most well-known preventative cancer vaccine is Gardasil, which was developed based on the virus-like particle of the major papillomavirus capsid protein L1.¹⁷ Currently, a therapeutic mRNA cancer vaccine against pancreatic cancer is also in development.¹⁸

7. Oncolytic viruses: Oncolytic viruses (OVs) are a form of immunotherapy. They selectively replicate within neoplastic cells, ultimately inducing tumor cell lysis. OVs can be genetically engineered to enhance tumor specificity, optimize replication, minimize off-target effects, and potentiate immune activation.¹⁹ While their primary mechanism involves direct tumor cell lysis, OVs also exert several critical secondary effects. They can stimulate the immune system through the release of damage-associated molecular patterns, tumor-associated antigens, and proinflammatory cytokines from infected tumor cells. The FDA approved the first oncolytic virus in 2015 for melanoma treatment.²⁰

8. Antibody–drug conjugates: These so-called smart chemotherapies combine a monoclonal antibody with a cytotoxic agent to target tumors directly while minimizing damage to healthy cells.²¹ The concept was first proposed over a century ago by Nobel Prize-winning scientist Paul Ehrlich. Ongoing investigations focus on reducing side effects, improving tissue penetration, creating dual-payload systems, enabling dual-antigen targeting to address tumor heterogeneity, and expanding the use of antibody-drug conjugates beyond oncology.

How Do Biologics Compare to Traditional Cancer Therapies?

One major advantage of biologics over traditional therapies is their targeted action, particularly in cancer treatment.²² Conventional cytotoxic chemotherapies tend to affect both cancerous and healthy cells, resulting in widespread toxicity. This not only causes well-known side effects like hair loss but also damages vital organs such as the heart, lungs, and reproductive system. In contrast, biologics offer greater precision, helping to minimize harm to normal cells while enhancing the selectivity of their anti-tumor effects. Currently, biologics are often used alongside traditional cancer treatments rather than as stand-alone monotherapies.

Given the wide variety of biologics and the diverse range of cancers they target, it is challenging to make broad generalizations about their efficacy, especially in such a rapidly evolving and still-emerging field. Some biologics, particularly monoclonal antibodies, have become mainstays of treatment; for example, trastuzumab has significantly improved outcomes for patients with HER2-positive breast cancer.²³

The Future of Biologics

The biologics field is rapidly evolving, with vast potential still to be unlocked. Future efforts will focus on improving accessibility, safety, and efficacy. Researchers are developing more patient-friendly delivery methods, such as oral, topical, and inhaled formulations, to supplement traditional injections and transfusions. Minimizing unwanted immune reactions remains a critical challenge. Meanwhile, cutting-edge technologies such as nanomedicine and precision medicine are enabling more effective treatments. Innovations in multivalent and multispecific therapeutics promise to expand targeting capabilities, further enhancing treatment effectiveness.