Immunotherapy: Immune Sera and Immunoglobulins

Immunotherapy: Immune Sera and Immunoglobulins

  • Immunotherapy means treatment of infectious, autoimmune or cancer diseases with versatile immunobiological products or chemical drugs that influence the state of the immune system.
  • It is further divided into activation and suppression immunotherapy. A special field is passive immunotherapy that can be regarded as substitution immunotherapy.
  • Activation immunotherapy comprises the treatment measures that stimulate or enhance host immune response.
  • A great variety of substances is employed for activation immunotherapy.
  • Among them are the vaccines used for therapeutic objectives (e.g., intravesical treatment of bladder cancer with BCG vaccine) and numerous products of recombinant cytokines (IL-1β or betaleukin, IL-2 or ronkoleukin, colony-stimulating factors like G-CSF or filgrastim, recombinant alpha- and beta-interferons, recombinant chemokines and many others) as well as chemical synthetic drugs for immune stimulation (e.g., imiquimod that activates innate immune response via TLR7).
  • By contrast, suppression immunotherapy presumes the treatment that inhibits host immune reactions.
  • To aim this, various medications are used. For instance, numerous groups of cytostatic drugs are applied for chemotherapy of cancer (methotrexate, cisplatin and many others); immunophilins (ciclosporin, tacrolimus and rapamycin) inhibit T cells, thus preventing allograft rejection and autoimmune disease progression; glucocorticoids and therapeutic humanized monoclonal antibodies are used in all of these clinical situations.
  • Passive immunotherapy means treatment or prevention of diseases by immunobiological products (e.g., immune sera, immunoglobulins and antibodies, cytokines, immune cells and others) obtained from external sources to create artificial passive immunity.
  • Passive immunotherapy replenishes the immune factors, which are deficient in the patient’s body.
  • Immune serum for passive immunotherapy is produced by host immunization with the corresponding antigen. These sera contain specific antibodies against the pathogenic agent.
  • Immunoglobulins are derived from immune sera after additional purification. They can be isolated from several sources – animals (e.g., horses) or humans (blood donors or healthy volunteers).
  • Immune sera are divided into antitoxic and antimicrobial.
  • Antitoxic sera include anti-diphtheritic, antitetanic serum, immune serum against botulotoxin, anaerobic clostridial infections, snake venoms, etc. Antimicrobial serum may be used against anthrax or some other diseases.
  • Therapy with horse immune serum can provoke serious complications during the treatment course. It depends on the foreign nature of injected proteins. In the case of massive antigenic exposure, the immune response to horse serum proteins is triggered, and serum sickness can develop.
  • In order to prevent these adverse effects, the administration of immunoglobulins instead of sera is preferable.
  • Immunoglobulins (or gamma globulins) are usually of human origin. They are obtained from blood donors and used for curative and prophylactic purposes against measles, poliomyelitis, whooping cough, viral hepatitis A and B, etc. Specific gamma globulin is also administered together with a vaccine against rabies.
  • Highly active immunoglobulins with direct protective effect are produced against staphylococcal toxin. They are isolated from donors immunized with staphylococcal toxoid.
  • Isolated immunoglobulins tend to form a lot of minute aggregates, and this may cause serious anaphylactic reactions. To prevent undesirable effects, the material should be injected intramuscularly.
  • Nevertheless, modern Ig products free of aggregates are available now. They are generally known as immunoglobulins for intravenous injection (or IVIGs). Such immunotherapeutic drugs contain higher titers of antibodies and can be used for the treatment of severe disorders, including profound immunodeficiency, septicemia and autoimmune thrombocytopenia.
  • The most recent advances in passive immunotherapy are related to the development of therapeutic monoclonal antibodies (mAbs). They notably expanded the opportunities for successful control of human cancer and autoimmune diseases. Because of their strict specificity and selectivity, the treatment with therapeutic mAbs is called “targeted therapy”.
  • However, there were many primary difficulties in this way, as standard murine mAbs rapidly trigger an immune response when administered to the human hosts. Therefore, the procedure of “humanization” of monoclonal antibodies becomes mandatory that substitutes antibody sequences of murine origin with human ones. It can be performed, for example, by the design of phage genetic libraries of active sites of human antibodies by methods of genetic engineering. Similarly, the “humanized” constant parts of antibodies can be produced.
  • As a result, a broad panel of therapeutic monoclonal antibodies is introduced into clinical practice nowadays. Among them are powerful anti-cancer tools like trastuzumab (mAb against specific receptor of breast cancer cells) or rituximab (anti-CD20 mAb active against human lymphomas) as well as the remedies against autoimmune diseases – infliximab (mAb against TNF-α), tocilizumab (mAb directed against IL-6 receptor) and many others. These perspective investigations are in great progress now.