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Oncolytic virus

Oncolytic virus

Limitations of existing anti-cancer drugs

ㆍFirst generation of cancer drugs were mostly small molecule chemotherapeutics with minimal cancer-targeting capability, 2nd generation was comprised of tumor-targeted therapeutics (e.g., monoclonal antibodies), and the 3rd generation drugs (immunotherapeutics) have focused on restoring and boosting patient’s immune system to precisely eliminate tumor cells. Although significant advancements in potency and safety profile have been achieved over the years, all generation of cancer drugs have distinct limitations and fails to meet the unmet needs of many cancer patients.

ㆍChemotherapeutics have excellent cancer cell killing effect in vitro, but show poor tumor specificity, indiscriminately destroy normal cells, and cause severe side effects in patients

ㆍTargeted therapeutics and immunotherapeutics have fewer side effects than chemotherapeutics due to markedly improved tumor specificity, but both therapeutics are only beneficial in a small subset of cancer patients with tumors expressing a complementary surface surface marker or immunologically hot tumors, respectively.

ㆍDespite their relative success, tumor recurrence and metastasis are observed in patients who initially responded well to targeted therapeutics and only a small subset of patient show good response toward immunotherapy

ㆍOncolytic viruses have emerged as novel therapeutics that will address these unmet needs of cancer patients

Functions of Oncolytic Virus

ㆍOncolytic viruses selectively replicate in and lyse tumor cells, which eventually cause secondary and tertiary infection of neighboring tumor cells and their eventual destruction

ㆍOncolytic viruses are designed to exhibit diminished replication capacity in normal cells, thus minimizing the side effects

ㆍOncolytic viruses are capable of inducing tumor-specific immune responses both locally at the injected site and non-injected distal metastases

Obstacles to Oncolytic Virus

ㆍAlthough oncolytic viruses have many advantages over the conventional cancer treatment options, they still have some limitations that must be overcome to maximize their therapeutic potential in clinical environment
  • Insufficient tumor specificity

    Although most conventional oncolytic viruses replicate selectively in tumor cells, they still indiscriminately infect normal cells, thus resulting in poor therapeutic effect and off-target cytotoxicity

  • Inadequate internalization into tumor cells

    Insufficient internalization and infection of tumor cells throughout the tumor bed leads to incomplete destruction of tumor that eventually promote tumor recurrence and unsatisfactory anti-metastatic effect

  • Suboptimal virus distribution throughout the tumor

    Tumor microenvironment contains aberrantly dense extracellular matrix (ECM) that acts as a physical barrier, which ultimately limits the dispersion of conventional oncolytic viruses in tumor tissues

  • Poor systemic administrability

    Intratumoral administration of conventional oncolytic viruses fail to adequately treat metastatic or inaccessible tumors. However, systemic administration of conventional oncolytic viruses causes adverse inflammatory response and nonspecific accumulation of the virus in normal tissues, thus resulting in undesirable side effects