Cancer Vaccines: Preventing and Treating Cancer

Cancer vaccines have traditionally been divided into two categories:
prophylactic anti-viral vaccines and therapeutic anti-tumor vaccines.

Prophylactic vaccines target oncogenic viral infections to eliminate the cancer-causing agent before a tumor can form. About 10% of all cancers worldwide are attributable to viral infection.¹The only two FDA-approved prophylactic cancer vaccines are Gardacil and Cervarix, both of which target specific strains of human papillomavirus (HPV) that cause most cases of cervical cancer.

Therapeutic cancer vaccines are designed to generate a targeted, immune-mediated antitumor response. The challenge in designing successful anti-tumor vaccines is to select a specific antigen, usually a protein expressed only by cancer cells and not by healthy cells, to avoid dangerous widespread autoimmunity. The only currently FDA-approved vaccine for cancer therapy is Sipuleucel-T (Provenge^®), which heightens dendritic cells responses to prostatic acid phosphatase, a protein overexpressed by prostate cancer cells. Antitumor vaccines in development employ several different types of antigens, including resected tumor cells, purified peptide antigens, DNA encoding antigens to prolong the antigen-stimulated immune response, and sometimes viral or cellular vectors.²

GenScript Offers Services to Support Vaccine Research and Development

While the success of HPV vaccines and cancer immunotherapies have buoyed hopes for vaccines to prevail in the war on cancer, must basic and translational research remains to be done – and GenScript is committed to providing services that will accelerate future discoveries.

Vaccine research can be aided by Gene Synthesis of Codon-Optimized sequences to promote immune-stimulatory antigen expression. Mutagenesis remains the gold standard for demonstrating specificity of antigenic epitopes, and mutant libraries are powerful tools for screening protein variants to engineer or discover optimal antigens. Gene Synthesis enables custom design of powerful DNA vaccines that combine high-level expression of antigenic transgenes and cytokine genes in safe, efficacious vectors. De novo gene synthesis gives you complete flexibility and control of your DNA sequences so that you can optimize the safety and efficacy of DNA-based vaccines with respect to the vector, the transgene, adjuvants, and other elements that influence gene transfer efficacy, therapeutic gene expression levels, immune responses, and risk of recombination. GenScript's vast experience with gene synthesis of DNA vaccines and vectors allows us to provide customized solutions to meet your research needs.

Vaccine research can also be aided by custom peptides and custom peptide libraries which are key tools for antigen epitope mapping in early vaccine development. Peptides represent the minimum antigenic region on a viral protein, making them suitable for directed immune response as vaccines. Additionally, peptide vaccines are attractive because they are relatively safe and easy to produce. GenScript offers custom peptide libraries that can contain hundreds of peptides for epitope screening assays. GenScript also offers custom peptide synthesis for the synthesis of complex peptides to serve as single or cocktail vaccines as well as MAPS multivalent peptides for increased antigenicity.

In addition, GenScript offers custom polyclonal and monoclonal antibody production. There are many advantages to using custom peptides instead of traditional full-length proteins as antigens, and GenScript has developed cutting edge technologies to drastically improve the success of choosing peptide sequences which result in custom antibodies recognizing natively folded proteins. Antibodies in the commercial pipeline for cancer are increasingly non-canonical – such as bispecific Abs, glycoengineered Abs, and antibody fragments – indicating that these may be more advantageous than the traditional full-length antibodies.

Case Studies

Recent Studies on Cancer Vaccines that employed Gene Synthesis from GenScript include

Comparison of Adenoviruses as Oncolytics and Cancer Vaccines in an Immunocompetent B Cell Lymphoma Model.
Weaver EA, Chen CY, May SM, Barry ME, Barry MA.Hum Gene Ther. 2011 Sep;22(9);1095-1100

• Research Highlights: Examples of how Gene Synthesis Powers Novel Findings for Vaccine Design

  Synthetic modified viral sequences produce safer, more effective DNA vaccines.

  Diniz et al. report in Human Gene Therapy that codon optimization augmented both the immunogenicity and the therapeutic anti-tumor effects induced by a DNA vaccine targeting human papillomavirus (HPV)-induced tumors. At the same time, introducing specific point mutations into a viral sequence, such as the modification of the E7 protein sequence found in HPV, can abolish residual oncogenic effects rendering the vaccine less likely to cause harm.

  Gene synthesis of codon-optimized antibodies allow isolation of viral epitopes for structural study and rational design of more potent drugs

  A recent Science paper reports the discovery of a novel antigenic site for respiratory syncytial virus (RSV) that will enable rational design of vaccine antigens. Using synthetic codon-optimized heavy and light chains of antibodies that bind the RSV F glycoprotein in its prefusion state, McLellan et al. obtained the first crystal structure of the metastable prefusion conformation of RSV F. This structural characterization allowed them to identify a novel antigenic site, termed "site Ø". Antibodies targeting site Ø are extremely potent, and hold promise to reduce the morbidity and mortality of this ubiquitous childhood virus.