Efficacy Evaluation of Activated Lymphocyte Therapy

【A report was published on the use of activated lymphocytes to improve the quality of life of cancer-bearing dogs!!】

Quality of life-improving effect of autologous ex vivo expanded cytotoxic and opioid-producing lymphocytes for dogs with cancers.
Mitani K, Ito Y, Takene Y, Hatoya S, Sugiura K, Inaba T.
Veterinary Immunology and Immunopathology 238: 110292 (2021)

Activated Autologous Lymphocyte Therapy

  • One of the immunotherapies against cancer.
  • Peripheral blood lymphocytes are isolated from dogs with cancer and cultured with anti-CD3 antibody and interleukin (IL)-2 to produce activated lymphocytes with enhanced activity against cancer cells.
  • Lymphocytes are collected and administered to cancer-affected dogs for treatment.
  • This therapy is known to prolong life and improve quality of life in B-cell lymphomas.

Issues in validity evaluations to date

  • There are no objective criteria for evaluating quality of life.
  • Improvement in quality of life is not an accepted measure of treatment efficacy.

Pain of the owner

Improving the quality of life of affected dogs is an important issue.

Methods of assessing quality of life with objectivity

Canine Health-related QOL Survey-15（CHQLS-15）　Lavan., Vet. J. 2013

Characteristics

  1. Easily assessable by the owner.
  2. It quantitatively captures health conditions related to daily life that can be objectively assessed without disease-specific endpoints.
  3. Evaluations can be made by the owner, who can observe at all times, to ensure consistent standards with no change in evaluators.

Ability of activated lymphocytes

  1. IFN-ɤ production to increase the ability to attack cancer cells
  2. Proenkephalin production, one of the opioids that exerts analgesic effects

Flow of activated lymphocytes from culture to treatment

  1. Isolation of mononuclear cells (PBMCs) from peripheral blood collected from 58 dogs with malignant tumors by density gradient centrifugation
  2. Activated lymphocytes were cultured with solid-phase anti-canine CD3 antibody and human recombinant IL-2 for 2 weeks.
  3. For treatment, the resulting cells were suspended in 50 ml of saline and administered intravenously by intravenous infusion over approximately 1 hour.
  4. This treatment was performed maximum 6 times at 2-week intervals from blood collection to administration.

Number of cases of activated autologous lymphocyte therapy

Quality of life changes in four areas

Significant increases in quality of life in all four areas were observed with each successive course of activated lymphocyte therapy.

Overall QOL change

Cases in which an increase in QOL was observed tended to have higher owner satisfaction with treatment.

 

Conclusion

  • By applying an objective quality of life assessment method (CHQLS-15), activated autologous lymphocyte therapy was proven to improve the quality of life of cancer-affected dogs.
  • As a possible mechanism, the involvement of endogenous opioids produced by activated lymphocytes was suggested.

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