Combinatorial ablation and immunotherapy explained

Combinatorial ablation and immunotherapy
Specialty:oncology

Combinatorial ablation and immunotherapy is an oncological treatment that combines various tumor-ablation techniques with immunotherapy treatment.[1] [2] [3] [4] Combining ablation therapy of tumors with immunotherapy enhances the immunostimulating response and has synergistic effects for curative metastatic cancer treatment.[2] [3] Various ablative techniques are utilized including cryoablation, radiofrequency ablation, laser ablation, photodynamic ablation, stereotactic radiation therapy, alpha-emitting radiation therapy, hyperthermia therapy, HIFU.[5] [6] [7] [8] [9] Thus, combinatorial ablation of tumors and immunotherapy is a way of achieving an autologous, in-vivo tumor lysate vaccine and treating metastatic disease.

Mechanism of action

Take magnetic hyperthermia for example. By applying magnetic nanoparticle-mediated hyperthermia with a threshold of 43 °C in order not to damage surrounding normal tissues, a significant quantity of heat-shock proteins (HSP) is expressed within and around the tumor tissues, inducing tumor-specific immune responses. In vivo experiments have indicated that magnetic nanoparticle-mediated hyperthermia can induce the regression of not only a local tumor tissue exposed to heat, but also distant metastatic tumors unexposed to heat. Partially or entirely ablating primary or secondary metastatic tumors induces necrosis of tumor cells, resulting in the release of antigens and presentation of antigens to the immune system. The released tumor antigens help activate anti-tumor T cells, which can destroy remaining malignant cells in local and distant tumors. Combining immunotherapy (ie: checkpoint inhibitors, CAR-T cell therapy) and vaccine adjuvants (ie: interferon, saponin) with ablation synergizes the immune reaction, and can treat metastatic disease with curative intent.[10] [11] [12] [13] [14]

Ablation therapies

Various local ablation therapies exist to induce necrosis of tumor cells and release tumor antigens to stimulate an immunological response. These ablation therapies can be combined with a systemic immunotherapy:

See also

Notes and References

  1. Dupuy. et al . Thermal ablation of tumours: biological mechanisms and advances in therapy. Nature Reviews Cancer. 14. 3. 199–208. 2014. 10.1038/nrc3672. 24561446. 9224039 .
  2. Thermal Ablative Therapies and Immune Checkpoint Modulation: Can Locoregional Approaches Effect a Systemic Response?. 2015. 10.1155/2016/9251375. free. Mehta. Amol. Oklu. Rahmi. Sheth. Rahul A.. Gastroenterology Research and Practice. 2016. 1–11. 27051417. 4802022.
  3. Web site: Immunotherapy could transform systemic power of locoregional IO treatments. 2016. 2017-05-03. 2020-12-01. https://web.archive.org/web/20201201212056/https://interventionalnews.com/immunotherapy-could-transform-systemic-power-of-locoregional-io-treatments/. live.
  4. Book: Cancer Immunology and Immunotherapy. 2016. 218. 9783642141362. Dranoff. Glenn. Springer. 2021-10-18. 2021-03-17. https://web.archive.org/web/20210317184001/https://books.google.com/books?id=XSM545kh36oC&pg=PA218%2F. live.
  5. Web site: Prof. Yona Keisari . Development of Cancer Treatments Integrating Radiotherapy or Electrochemical Ablation and Immunotherapy . 2017-05-03 . 2018-03-17 . https://web.archive.org/web/20180317232104/https://en-med.tau.ac.il/research_ablation . live .
  6. 2003 . Tumor regression by combined immunotherapy and hyperthermia using magnetic nanoparticles in an experimental subcutaneous murine melanoma . Cancer Science . 94 . 3 . 308–13 . 12824927 . Ito . A . Tanaka . K . Kondo . K . Shinkai . M . Honda . H . Matsumoto . K . Saida . T . Kobayashi . T . 10.1111/j.1349-7006.2003.tb01438.x . free . 11160160 .
  7. Xiaoming Yang . 2016 . Radiofrequency hyperthermia promotes the therapeutic effects on chemotherapeutic-resistant breast cancer when combined with heat shock protein promoter-controlled HSV-TK gene therapy: Toward imaging-guided interventional gene therapy . Oncotarget . 7 . 40 . 65042–65051 . 10.18632/oncotarget.11346 . 27542255 . 5323137 .
  8. 2000 . Eradication of breast cancer xenografts by hyperthermic suicide gene therapy under the control of the heat shock protein promoter . Human Gene Therapy . 11 . 18 . 2453–63 . 11119417 . Braiden . V . Ohtsuru . A . Kawashita . Y . Miki . F . Sawada . T . Ito . M . Cao . Y . Kaneda . Y . Koji . T . Yamashita . S . 10.1089/10430340050207948 .
  9. Book: 2016 . Hyperthermic Oncology from Bench to Bedside . 319–327 . 10.1007/978-981-10-0719-4_30 . Combination by Hyperthermia and Immunotherapy: DC Therapy and Hyperthermia . Takeda . Tsutomu . Takeda . Takashi . 978-981-10-0717-0 .
  10. 2015 . Cryo-thermal therapy elicits potent anti-tumor immunity.. Scientific Reports. 6. 1. 27136. 10.1038/srep27136. Zhu. Jun. Zhang. Yan. Zhang. Aili. He. Kun. Liu. Ping. Xu. Lisa X.. 27256519. 4891716.
  11. Cryosurgery initiates inflammation and leaves tumor-specific antigens intact, which may induce an anti-tumor immune response.2005 . Immunologic response to cryoablation of breast cancer . Sabel . 4115762 . 25083502 . 10.3978/j.issn.2227-684X.2014.03.04 . 3 . 2 . Gland Surg . 88–93.
  12. 2005. Combined Dendritic Cell Cryotherapy of Tumor Induces Systemic Antimetastatic Immunity.. 10.1158/1078-0432.CCR-04-2422. Machlenkin. A.. Goldberger. O.. Tirosh. B.. Paz. A.. Volovitz. I.. Bar-Haim. E.. Lee. S. H.. Vadai. E.. Tzehoval. E.. Eisenbach. L.. Clinical Cancer Research. 11. 13. 4955–4961. 16000595. 15624452. free. 2017-05-04. 2019-08-06. https://web.archive.org/web/20190806094619/http://clincancerres.aacrjournals.org/content/11/13/4955. live.
  13. 2016 . Thermal Ablative Therapies and Immune Checkpoint Modulation: Can Locoregional Approaches Effect a Systemic Response. Gastroenterol Res Pract . 10.1155/2016/9251375 . 27051417. 4802022. 2016 . 1–11. Mehta. Amol. Oklu. Rahmi. Sheth. Rahul A.. free.
  14. 2012 . Nanoparticle-mediated hyperthermia in cancer therapy. . Therapeutic Delivery . 2 . 8 . 1001–1014 . 3323111 . Chatterjee . D. K. . Diagaradjane . P. . Krishnan . S. . 22506095 . 10.4155/tde.11.72 .
  15. Arazi . Lior . Treatment of solid tumors by interstitial release of recoiling short-lived alpha-emitters . Phys. Med. Biol. . 2007 . 52 . 16 . 5025–5042 . 10.1088/0031-9155/52/16/021 . 17671351 . 2007PMB....52.5025A . 1585204 . May 24, 2020.
  16. Cooks . Tomer . Growth retardation and destruction of experimental squamous cell carcinoma by interstitial radioactive wires releasing diffusing alpha-emitting atoms . Int. J. Cancer . 2008 . 122 . 7 . 1657–1664 . 10.1002/ijc.23268 . 18059026 . free .