Biopharma

The field of Biopharmaceuticals (Biopharma) encompasses biologic-type therapeutics to tackle complex diseases. Biologic-type therapeutics can be either one of the following: 1) protein-based therapeutics (recombinant proteins made by engineered cells in bioreactors), 2) gene therapies, 3) cell therapies. Biopharma therapeutics are prescribed by a physician and delivered bedside from a sterile vial or bag.

Protein-based therapeutics can be enzymes, vaccines, monoclonal antibodies, or polyclonal antibodies, mono-specific/bi-specific/tri-specific antibodies, peptides, hormones (i.e. insulin and GLP), stimulating factors, and inhibitors (blockers).

Gene therapies encompass naked RNA, naked iRNA (interference RNA), nacked DNA, RNA/DNA encapsulated (as cargo) in a vector. Gene therapies deliver a missing (or mutated) gene to the patient.

Vectors can be viral vectors (engineered viruses to be nonpathogenic and to act as delivery vehicles to a target cell), or non-viral vectors.

Viral Vectors

• Adeno-associated virus (AAV): Popular for gene therapy due to low immunogenicity and stable expression.

• Adenovirus (AdV): High transduction efficiency, but more immunogenic.

• Herpes simplex virus (HSV): Useful for neurological applications because of its neurotropism.

• Retrovirus & Lentivirus: Retroviruses integrate into host genomes; lentiviruses (i.e. HIV-derived) can transduce non-dividing cells, making them critical for CAR-T and stem cell therapies.

• Baculovirus: Often used in vaccine production and protein expression systems. Baculoviruses only infect and replicate in insect cells.

Non-Viral Vectors

• Exosomes: Natural extracellular vesicles (EVs) with strong biocompatibility, emerging in RNA and protein delivery.

• Lipid nanoparticles (LNPs): Central to mRNA vaccines.

• Liposomes: Classic lipid-based carriers, precursors to LNPs.

• Polymeric nanoparticles: Synthetic polymers (i.e. polyethylenimine, PLGA) for DNA/RNA delivery.

• Peptide-based carriers: Cell-penetrating peptides (CPPs) enhance intracellular delivery.

• Hybrid systems: Combinations of biological and synthetic elements (i.e. virus-like particles, biomimetic nanoparticles).

Vectors can be used to create cell therapies, by genetically modifying the cell to be used as a therapy (either in-vivo or ex-vivo (in-vitro)), so the cell can express a therapeutic molecule of interest. The cell can be modified permanently (by modifying its genome), or can be modified in an episomal form (to avoid modifying the genome).

Categories of Cell Therapies:

• Stem Cell Therapies

• Hematopoietic stem cells (HSCs), mesenchymal stromal cells (MSCs), induced pluripotent stem cells (iPSCs)

• Applications: blood cancers, immune deficiencies, regenerative medicine

• CAR-T Cell Therapies

• Autologous or allogeneic CAR-T cells

• Applications: hematologic malignancies (i.e. B-cell leukemias, lymphomas)

• TCR Therapies

• Engineered T-cell receptor (TCR) therapies

• Applications: solid tumors, viral infections

• NK Cell Therapies

• Natural killer (NK) cells, CAR-NK cells

• Applications: cancer immunotherapy, viral infections

• Dendritic Cell Therapies

• Autologous dendritic cells

• Applications: cancer vaccines, immune modulation

• γδ T-Cell Therapies

• Non-conventional γδ T cells

• Applications: solid tumors, infectious diseases

• Other Mature Cell Therapies

• Pancreatic islet cells, chondrocytes, hepatocytes

• Applications: diabetes, cartilage repair, liver disease

• Bacterial Cell Therapies

• Engineered bacterial cells that penetrate the tumor micro-environment (TME) to bring a localized immune-system response around the tumor.

• Applications: solid-tumor cancers

The field of Immunology is intertwined with biopharma, medicine and pharmacy. Thus, it is critical to learn Immunology to embrace the Life Sciences.

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