The Latest Talk in Cancer Immunotherapy: A Brief Overview of Developments & Current Players in the Exosome Space

Exosomes are making waves in cancer research. These tiny vesicles, about 40-150 nanometers, carry proteins, nucleic acids, and lipids. They shuttle messages between cells, influencing everything from immune responses to tumor growth. However, they’re a double-edged sword—sometimes boosting immunity, other times helping cancer thrive. Let’s dive into how exosomes work, their dual roles in cancer immunotherapy, and real-world examples driving innovation.

What Are Exosomes and How Do They Work?

Exosomes act like cellular couriers. Cells release them to deliver cargo—think DNA, RNA, or proteins—to other cells. They form in three ways: through multivesicular bodies, budding within cell compartments, or directly from the plasma membrane. Once out, they interact with target cells via receptor binding, phagocytosis, or membrane fusion.

For example, Codiak BioSciences engineered exosomes to deliver precise therapeutic payloads. Their exoIL-12 platform targeted immune cells to fight tumors, showing how exosomes can pinpoint specific cells in the body.

The Dark Side: How Exosomes Help Cancer Grow

Exosomes can fuel cancer progression. Tumor-derived exosomes (TEXs) carry molecules like PD-L1, which suppress immune responses. They create a cozy tumor microenvironment (TME), helping cancer cells dodge immune attacks.

Promoting Blood Vessel Growth

TEXs spark angiogenesis, forming new blood vessels to feed tumors. They carry VEGF, a growth factor that signals endothelial cells to build vascular networks. For instance, ovarian cancer exosomes with E-cadherin trigger angiogenesis without VEGF, boosting tumor growth.

Evox Therapeutics uses exosome tech to tackle this. Their platform delivers RNA therapies to disrupt angiogenesis, aiming to starve tumors by cutting their blood supply.

Setting Up Metastatic Hideouts

TEXs prepare premetastatic niches, cozy spots for cancer to spread. They recruit immune cells and fibroblasts, remodeling tissues to welcome cancer cells. In pancreatic cancer, exosomal MIF triggers TGF-β release, paving the way for liver metastasis.

ILIAS Biologics counters this with exosomes loaded with anti-metastatic cargo. Their EXPLOR platform inhibits premetastatic niche formation, slowing cancer spread in preclinical models.

Rewiring Stromal Cells

Exosomes reshape stromal cells into tumor allies. They turn fibroblasts into cancer-associated fibroblasts (CAFs), which churn out immunosuppressive cytokines. Breast cancer exosomes, for example, deliver miR-92 to boost CAF activity, aiding tumor invasion.

Aruna Bio fights this with neural-derived exosomes. Their AB126 platform reprograms stromal cells to reduce tumor support, showing promise in glioblastoma models.

Reprogramming Metabolism

Cancer cells lean on exosomes to rewire metabolism. TEXs from breast cancer cells lower glucose use in fibroblasts via miR-122, favoring tumor-friendly glycolysis. This creates lactic acid, which weakens immune cells.

Exo Therapeutics targets metabolic reprogramming. Their exosome-based inhibitors block glycolysis pathways, aiming to restore immune function and halt tumor growth.

Helping Tumors Evade Immunity

TEXs excel at immune evasion. They express PD-L1, shutting down T cells. In lung cancer, exosomal circUSP7 blocks cytokine release from T cells, fostering resistance to anti-PD1 therapy.

Kimera Labs develops exosomes to counter this. Their MSC-derived exosomes carry immune-activating molecules, aiming to override tumor suppression in clinical trials.

The Bright Side: Exosomes as Cancer Fighters

Exosomes aren’t always villains. Immune cell-derived exosomes can rally the body’s defenses, turning the tide against cancer.

Flipping Macrophages to Attack Mode

M1 macrophage exosomes reprogram tumor-associated macrophages (TAMs) into cancer-killing M1 types. Breast cancer exosomes with miR-33 target TAMs, boosting M1 polarization via the MAPK pathway.

Codiak’s exoSTING platform amplified this. It delivered STING agonists to macrophages, flipping them to M1 and sparking antitumor immunity in solid tumors.

Presenting Antigens for Immune Activation

Dendritic cell exosomes (DEXs) shine in antigen presentation. They carry MHC molecules to activate T cells. In hepatocellular carcinoma, DEXs loaded with α-fetoprotein trigger robust CD8+ T cell responses, shrinking tumors.

Capricor Therapeutics harnesses this with their exosome-based vaccines. Their platform delivers tumor antigens to dendritic cells, boosting T cell responses in preclinical cancer models.

Delivering Cytotoxic Blows

NK cell exosomes pack a punch. They carry perforin and granzyme, directly killing tumor cells. Exosomal miR-186 from NK cells, for instance, slows neuroblastoma growth by targeting MYCN.

Omniscient Biotech uses NK-derived exosomes for cytotoxicity. Their OmniExo platform delivers miRNAs to tumors, enhancing NK cell-like killing in early trials.

Exosomes in the Real World: Biomarkers and Drug Carriers

Exosomes are stepping into clinical roles, serving as biomarkers and drug delivery vehicles.

Tracking Cancer and Treatment Success

Exosomes in blood or urine reveal cancer status. In lung cancer, exosomal miRNAs like hsa-miR-320d signal immunotherapy response. A trial (NCT05705583) tests exosomes as biomarkers for renal cell carcinoma immunotherapy outcomes.

ExoDx, by Bio-Techne, offers a commercial example. Their urine-based exosome test detects prostate cancer biomarkers, guiding treatment decisions with high accuracy.

Powering Precision Drug Delivery

Exosomes deliver drugs with pinpoint accuracy. Their biocompatibility and targeting ability make them ideal carriers. M1 macrophage exosomes modified with anti-CD47 antibodies, for example, boost phagocytosis in acidic tumor environments.

Carmine Therapeutics leads here. Their Red Cell EV platform engineers red blood cell-derived exosomes to deliver RNA therapies, targeting tumors with minimal toxicity in preclinical studies.

Challenges and the Road Ahead

Exosomes hold immense promise, but hurdles remain. Their heterogeneity complicates isolation and standardization. Non-autologous exosomes risk immune reactions, and loading them with drugs efficiently is tricky. Clinical-grade production also faces technical barriers.

Still, companies like Codiak, Evox, and Aruna push forward. Ongoing trials, like NCT05854030 for NSCLC, test exosome safety and efficacy. Researchers aim to refine targeting and scale production, paving the way for personalized cancer therapies.

In short, exosomes are game-changers in immunotherapy. They can fuel cancer or fight it, depending on their source and cargo. With innovators like Kimera Labs and Capricor advancing the field, exosomes are poised to transform cancer care, offering hope for more effective, tailored treatments.

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Author

Bernice Lottering