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Vaccine Therapy and antisense oligonucleotides

Advantages over passive immunity

  • Sustained response
  • Vaccine contains more than single determinant of target antigen
  • More than single epitope in a particular antigen can be identified by active immunity.
  • Vaccines activate both B and T lymphocytes

 

Components of therapeutic cancer vaccine

  • Antigenic material derived from the tumor- Usually it is over-expressed in tumor cells and is essential for tumor cell survival.
  • Carrier- Necessary to deliver tumor antigen to antigen presenting cell (Dendritic cell). Example: Liposomes, Mannose etc.
  • Adjuvant- Facilitates an enhanced immune response against the tumor antigen. Ex: Alum.

 

Impediments in vaccine therapy

  • Problems with trafficking of anti-tumor T cells to tumor site
  • Impaired function of antitumor T cells due to immunosuppressive mechanisms developed by tumor in its microenvironment.

 

Antisense oligonucleotides:

  • Expression of oncogene initiates the process of genesis of malignancy
  • Suppression of this expression can result in suppression of tumor growth
  • mRNA expression can be suppressed using antisense oligonucleotides.
  • They are short pieces of single stranded DNA or RNA (about 17-20 base pairs) which bind to translation initiation site of mRNA (as they contain complementary sequence)
  • They are being tried even in some benign diseases such as sickle cell anemia.
  • Example: Antisense nucleotides targeting BCL2 decrease the expression of BCL2. Hence cell becomes susceptible to apoptosis. Ex: Oblimerson in treatment of CLL.

 

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