Treatment outcome in a patient with triple-negative breast cancer using adoptive immunotherapy
https://doi.org/10.15789/1563-0625-TOI-3125
Abstract
Breast cancer (BC) is the most common malignant neoplasm in women. Adoptive immunotherapy (AIT) using activated lymphocytes is a promising approach to the treatment. Patient O., 63 years old, was diagnosed in October 2021 with infiltrating ductal carcinoma of left breast T3NxM0, Grade 2, triple negative subtype, CHEK-2 associated. According to PET/CT, the tumor size was 43 ´ 21 mm. AIT with cytokineinduced killers (CIK) was administered. In order to produce CIK, mononuclear cells were isolated from peripheral blood and cultured in presence of cytokines for 10-14 days. AIT was performed by intradermal injections paravertebrally once a week up to present date. In the course of AIT, PET/CT, MRI, ultrasound and immunophenotyping of blood lymphocytes were performed. 7 courses of AIT were administered since November 2021. Six months after starting AIT, positive dynamics was noted as proven by PET/CT data: a decreased activity of tumor in left mammary gland (LMG) with SUVmax of 16.76 (previously, SUVmax 28.74) while maintaining the size. Moreover, previously identified signs of osteoblastic changes in spine at Th12 level were not detected. According to PET/CT results in November 2022, a slight increase in size of LMG formation up to 49 ´ 35 mm (SUVmax, 16.82) was noted, while an area of the radiopharmaceutic accumulation was detected in the body of the L2 vertebra and sigmoid colon. Radical mastectomy was performed In early December 2022. The tumor size was 5.3 cm, the resection margin was free of tumor cells, metastases were found in 2 of 14 lymph nodes. In order to prevent relapse, AIT was continued: 790 million CIKs were administered during a year. According to MRI data in March 2023, there was no relapse. In August 2024, the lesion in the ileum still remains. The median overall survival of patients with TNBC is 10.2 months. The average life expectancy of patients with metastases is less than 1 year. In the presented clinical case, 34 months have passed since the diagnosis, thus indicating an effective combination of AIT with surgical treatment. We conclude that AIT CIKs has a high potential for treatment of patients with TNBC.
About the Authors
E. V. AbakushinaRussian Federation
Abakushina Elena V., PhD, MD (Medicine), Head, Department for Development and Research in Immunology, Deputy General Director, LLC “Tecon Medical Devices”; Head, Laboratory of Immunology and Autoimmune Diseases, Department of Molecular Oncology and Immunology, National Medical Research Center of Endocrinology
Moscow
R. V. Zhurikov
Russian Federation
Zhurikov Ruslan V., Researcher, Department for Development and Research in Immunology
Moscow
S. A. Roumiantsev
Russian Federation
Rumiantsev Sergey A., PhD, MD (Medicine), Professor, Head, Department of Molecular Oncology and Immunology, National Medical Research Center of Endocrinology; Head, Department of Oncology, Hematology and Radiotherapy, Institute of Motherhood and Childhood, N. Pirogov Russian National Research Medical University
Moscow
References
1. Abakushina E.V., Gelm Yu.V., Pasova I.A., Bazhin A.V. Immunotherapeutic Approaches for the Treatment of Colorectal Cancer. Biokhimiya = Biochemistry (Moscow), 2019, Vol. 84, no. 7, pp. 720-728. (In Russ.)
2. Abakushina E.V., Pasova I.A., Marizina Yu.V., Kudryavtsev D.V., Kudryavtseva G.T., Fomina E.S. Efficiency of adoptive immunotherapy for melanoma: a case report. Sibirskiy onkologicheskiy zhurnal = Siberian Journal of Oncology. 2016, Vol. 15, no. 5, pp. 89-94. (In Russ.)
3. Gel’m Y.V., Kuz’mina E.G., Abakushina E.V. Functional activity of lymphocytes of healthy donors and cancer patients after culturing with IL-2 and IL-15. Byulleten eksperimentalnoy biologii i meditsiny = Bulletin of Experimental Biology and Medicine, 2019, Vol. 167, no. 4, pp. 486-491. (In Russ.)
4. Bonotto M., Gerratana L., Poletto E., Driol P., Giangreco M., Russo S., Minisini A.M., Andreetta C., Mansutti M., Pisa F.E., Fasola G., Puglisi F. Measures of outcome in metastatic breast cancer: insights from a realworld scenario. Oncologist, 2014, Vol. 19, no. 6, pp. 608-615.
5. Dass S.A., Tan K.L., Selva Rajan R., Mokhtar N.F., Mohd Adzmi E.R., Wan Abdul Rahman W.F., Tengku Din TADA, Balakrishnan V. Triple negative breast cancer: a review of present and future diagnostic modalities. Medicina (Kaunas), 2021, Vol. 57, no. 1, 62. doi: 10.3390/medicina57010062.
6. Jia H., Truica C.I., Wang B., Wang Y., Ren X., Harvey H.A., Song J., Yang J.M. Immunotherapy for triplenegative breast cancer: Existing challenges and exciting prospects. Drug Resist. Updat., 2017, Vol. 32, pp. 1-15.
7. Li Y., Zhang H., Merkher Y., Chen L., Liu N., Leonov S., Chen Y. Recent advances in therapeutic strategies for triple-negative breast cancer. J. Hematol. Oncol., 2022, Vol. 15, no. 1, 121. doi: 10.1186/s13045-022-01341-0.
8. Liu S., Galat V., Galat Y., Lee Y.K.A., Wainwright D., Wu J. NK cell-based cancer immunotherapy: from basic biology to clinical development. J. Hematol. Oncol., 2021, Vol. 14, no. 1, 7. doi: 10.1186/s13045-020-01014-w.
9. Lu B., Natarajan E., Balaji Raghavendran H.R., Markandan U.D. Molecular classification, treatment, and genetic biomarkers in triple-negative breast cancer: a review. Technol. Cancer Res. Treat., 2023, Vol. 22, 15330338221145246. doi: 10.1177/15330338221145246.
10. Melsen J.E., Lugthart G., Lankester A.C., Schilham M.W. Human circulating and tissue-resident CD56(bright) Natural Killer cell populations. Front. Immunol., 2016, Vol. 30, no. 7, 262. doi: 10.3389/fimmu.2016.00262.
11. Myers J.A., Miller J.S. Exploring the NK cell platform for cancer immunotherapy. Nat. Rev. Clin. Oncol., 2021, Vol. 18, no. 2, pp. 85-100.
12. Sakach E., O’Regan R., Meisel J., Li X. Molecular classification of triple negative breast cancer and the emergence of targeted therapies. Clin. Breast Cancer, 2021, Vol. 2, no. 6, pp. 509-520.
13. Sanchez C.E., Dowlati E.P., Geiger A.E., Chaudhry K., Tovar M.A., Bollard C.M., Cruz C.R.Y. NK cell adoptive immunotherapy of cancer: evaluating recognition strategies and overcoming limitations. Transplant. Cell. Ther., 2021, Vol. 2, no. 1, pp. 21-35.
14. Shen M., Pan H., Chen Y., Xu Y.H., Yang W., Wu Z. A review of current progress in triple-negative breast cancer therapy. Open Med. (Wars.), 2020, Vol. 15, no. 1, pp. 1143-1149.
15. Veluchamy J.P., Kok N., van der Vliet H.J., Verheul H.M.W., de Gruijl T.D., Spanholtz J. The rise of allogeneic natural killer cells as a platform for cancer immunotherapy: recent innovations and future developments. Front. Immunol., 2017, Vol. 8, 631. doi: 10.3389/fimmu.2017.00631.
Supplementary files
Review
For citations:
Abakushina E.V., Zhurikov R.V., Roumiantsev S.A. Treatment outcome in a patient with triple-negative breast cancer using adoptive immunotherapy. Medical Immunology (Russia). 2025;27(4):873-880. (In Russ.) https://doi.org/10.15789/1563-0625-TOI-3125