Tumor-associated Antigen-loaded Oncolytic Vaccinia Virus
Creative Biolabs is an undoubted pioneer in the market of oncolytic vaccinia virus (VACV) development and enhancement. We provide a range of one-stop oncolytic VACV enhancement services, including tumor-associated antigen-loaded oncolytic VACV for our global customers.
VACV as Immunotherapeutic Cancer Vector
The ability of VACV to express tumor-associated antigens (TAAs) in their genome is employed for the development of immunotherapies for cancer to induce potent immune responses. The utility of VACVs as vehicles for cancer vaccines has been actively investigated over the last decades due to recombinant DNA technology. Genes encoding TAA can be inserted into viral vectors to generate effective immunogenic reagents. VACVs-based vectors are characterized by high immunogenicity and the capability of expressing various transgenes. Safety qualifies them as reagents of choice for immuno/gene therapy of various cancers due to their lack of integration into the host genome. With our comprehensive analysis, teams in Creative Biolabs are dedicated to offering you first-in-class TAA-loaded oncolytic VACV construction services to meet your goal of vaccinia virus development in a timely and cost-effective manner.
VACV Expressing TAA
- VACV Expressing Carcinoembryonic Antigen (CEA)
CEA is a well-characterized, biologically inert tumor marker with only minimal immunogenicity. It is commonly being used to monitor disease recurrence, most frequently in patients with colorectal cancer. Recombinant VACVs carrying CEA are constructed and examined in numerous preclinical studies. This VACV-CEA infection and propagation in cancer tissues results in CEA gene expression and secretion of the soluble marker protein into the extracellular space. VACV-CEA's first preclinical efficacy studies demonstrated considerable oncolytic potency of the virus in murine xenograft models of ovarian cancer and glioblastoma multiforme. Clinical trials have been conducted with these viruses to examine the toxicity, immune activities, and tumor responses in patients with advanced or metastatic CEA-expressing adenocarcinomas. The vaccines have been well-tolerated and effective at inducing CEA-specific cytotoxic T cell responses and anti-CEA antibodies. CEA measurement in the serum of treated patients may thus provide crucial feedback on the gene expression profile and viral kinetics of VACV-CEA during clinical testing.
- VACV Expressing Prostate-specific Antigen (PSA)
PSA is a glycoprotein expressed at a relatively low level by normal prostate epithelial cells. It is a good target for immunotherapy because most primary and metastatic prostate cancers commonly overexpress it. VACV encoding PSA (VACV-PSA) had demonstrated an ability to induce PSA-specific T cell responses and therapeutic activity in animal prostate cancer models, especially when cytokines and costimulatory molecules were co-expressed. A series of clinical studies in advanced-stage cancer patients have been performed using modified VACV encoding human PSA. A phase I clinical trial in patients with advanced or recurrent prostate cancer demonstrated that vaccination with VACV-PSA was well-tolerated, and successfully stimulated PSA-specific T cell production, and stabilized PSA levels. In addition, a therapeutic cancer vaccine consisting of poxviruses expressing a modified PSA has been tested in phase II clinical trials in patients with metastatic prostate cancer.
- VACV Expressing MART-1 and gp100
So far, many melanoma-associated tumor antigens have been identified. Among them, melanocyte differentiation antigens, such as MART-1, gp100, and tyrosinase, are most attractive as candidate targets for cancer immunotherapy as they are often expressed in most melanoma tumor cells. In numerous preclinical studies, VACV vectors expressing single melanoma TAAs or different combinations have demonstrated powerful capabilities to stimulate specific CTL generation and induce cytotoxicity against tumor cells that express the relevant antigens. In addition, some clinical studies are being conducted to evaluate the safety and immunogenicity of these vaccines. In general, these vaccines were well-tolerated and effective in generating cellular immune responses.
A recent report on a phase I/II clinical trial in metastatic melanoma patients with recombinant VACV expressing MART-1 minigene, peptides from gp100 and tyrosinase, and CD80 and CD86 costimulatory proteins showed that some patients had specific T cell responses against the TAAs. In this case, weak anti-tumor immune responses were observed in most patients. Adverse reactions were mild grade and mainly represented by fever, skin rashes, and pruritus. These data indicate that the administration of VACV encoding melanoma-associated epitopes and costimulatory molecules is safe and immunogenic. The immunization protocol appears to be well tolerated and can induce immune responses in metastatic melanoma patients.
As a global leader in oncolytic VACV development, Creative Biolabs provides a range of tumor-associated antigen-loaded oncolytic VACVs to meet your goal in a time-saving manner.