Open Access
Alloreactive Cellular Strategies for Targeted Leukemia Immunotherapy Via Transient Donor Cell Engagement
4
Division of Infectious Diseases, University of Toronto, Canada
4
Department of Immunology and Women’s Health, Qatar University, Doha, Qatar
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for hematological malignancies, with graft-versus-leukemia (GVL) effects playing a crucial role in disease eradication. This article reviews the principles of cellular immunotherapy, focusing on exploiting alloreactivity to induce anti-leukemic responses while minimizing prolonged donor cell persistence and associated graft-versus-host disease (GVHD). We discuss the mechanisms of alloreactivity, the clinical evidence supporting this approach, and future directions for optimizing cellular immunotherapy strategies.
Keywords
Allogeneic hematopoietic stem cell transplantation (allo-HSCT),
graft-versus-host disease (GVHD)
References
D’Orsogna, L.J.; Nguyen, T.H.; Claas, F.H.; Witt, C.; Mifsud, N.A. Endogenous-peptide-dependent alloreactivity: New scientific insights and clinical implications. Tissue Antigens 2013, 81, 399–407.
Blazar, B.R.; Murphy, W.J.; Abedi, M. Advances in graft-versus-host disease biology and therapy. Nat. Rev. Immunol. 2012, 12, 443–458.
Weiden, P.L.; Flournoy, N.; Thomas, E.D.; Prentice, R.; Fefer, A.; Buckner, C.D.; Storb, R. Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N. Engl. J. Med. 1979, 300, 1068–1073.
Kolb, H.J. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood 2008, 112, 4371–4383.
Bar, M.; Sandmaier, B.M.; Inamoto, Y.; Bruno, B.; Hari, P.; Chauncey, T.; Martin, P.J.; Storb, R.; Maloney, D.G.; Storer, B.; et al. Donor lymphocyte infusion for relapsed hematological malignancies after allogeneic hematopoietic cell transplantation: Prognostic relevance of the initial CD3+ T cell dose. Biol. Blood Marrow Transplant. 2013, 19, 949–957.
Dey, B.R.; McAfee, S.; Colby, C.; Cieply, K.; Caron, M.; Saidman, S.; Preffer, F.; Shaffer, J.; Tarbell, N.; Sackstein, R.; et al. Anti-tumour response despite loss of donor chimaerism in patients treated with non-myeloablative conditioning and allogeneic stem cell transplantation. Br. J. Haematol. 2005, 128, 351–359.
Rubio, M.T.; Kim, Y.M.; Sachs, T.; Mapara, M.; Zhao, G.; Sykes, M. Antitumor effect of donor marrow graft rejection induced by recipient leukocyte infusion in mixed chimeras prepared with nonmyeloablative conditioning: Critical role for recipient-derived IFN-gamma. Blood 2003, 102, 2300–2307.
Rubio, M.T.; Saito, T.I.; Kattleman, K.; Zhao, G.; Buchli, J.; Sykes, M. Mechanisms of the antitumor responses and host-versus-graft reactions induced by recipient leukocyte infusions in mixed chimeras prepared with nonmyeloablative conditioning: A critical role for recipient CD4+ T cells and recipient leukocyte infusion-derived IFN-gamma-producing CD8+ T cells. J. Immunol. 2005, 175, 665–676.
Saito, T.I.; Li, H.W.; Sykes, M. Invariant NKT cells are required for antitumor responses induced by host-versus-graft responses. J. Immunol. 2010, 185, 2099–2105.
Saito, T.I.; Rubio, M.T.; Sykes, M. Clinical relevance of recipient leukocyte infusion as antitumor therapy following nonmyeloablative allogeneic hematopoietic cell transplantation. Exp. Hematol. 2006, 34, 1271–1277.
Symons, H.J.; Levy, M.Y.; Wang, J.; Zhou, X.; Zhou, G.; Cohen, S.E.; Luznik, L.; Levitsky, H.I.; Fuchs, E.J. The allogeneic effect revisited: Exogenous help for endogenous, tumor-specific T cells. Biol. Blood Marrow Transplant. 2008, 14, 499–509.
Colvin, G.A.; Berz, D.; Ramanathan, M.; Winer, E.S.; Fast, L.; Elfenbein, G.J.; Quesenberry, P.J. Nonengraftment haploidentical cellular immunotherapy for refractory malignancies: Tumor responses without chimerism. Biol. Blood Marrow Transplant. 2009, 15, 421–431.
Guo, M.; Hu, K.X.; Yu, C.L.; Sun, Q.Y.; Qiao, J.H.; Wang, D.H.; Liu, G.X.; Sun, W.J.; Wei, L.; Sun, X.D.; et al. Infusion of HLA-mismatched peripheral blood stem cells improves the outcome of chemotherapy for acute myeloid leukemia in elderly patients. Blood 2011, 117, 936–941.
Guo, M.; Hu, K.X.; Liu, G.X.; Yu, C.L.; Qiao, J.H.; Sun, Q.Y.; Qiao, J.X.; Dong, Z.; Sun, W.J.; Sun, X.D.; et al. HLA-mismatched stem-cell microtransplantation as postremission therapy for acute myeloid leukemia: Long-term follow-up. J. Clin. Oncol. 2012, 30, 4084–4090.
Byrd, J.C.; Mrozek, K.; Dodge, R.K.; Carroll, A.J.; Edwards, C.G.; Arthur, D.C.; Pettenati, M.J.; Patil, S.R.; Rao, K.W.; Watson, M.S.; et al. retreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: Results from Cancer and Leukemia Group B (CALGB 8461). Blood 2002, 100, 4325–4336.
Fast, L.D. Recipient CD8+ cells are responsible for the rapid elimination of allogeneic donor lymphoid cells. J. Immunol. 1996, 157, 4805–4810.
Fast, L.D. Recipient elimination of allogeneic lymphoid cells: Donor CD4(+) cells are effective alloantigen-presenting cells. Blood 2000, 96, 1144–1149.
D’Orsogna, L.J.; van den Heuvel, H.; van der Meer-Prins, E.M.; Roelen, D.L.; Doxiadis, II; Claas, F.H. Stimulation of human EBV- and CMV-specific cytolytic effector function using allogeneic HLA molecules. J. Immunol. 2012, 189, 4825–4831.
Brehm, M.A.; Daniels, K.A.; Priyadharshini, B.; Thornley, T.B.; Greiner, D.L.; Rossini, A.A.; Welsh, R.M. Allografts stimulate cross-reactive virus-specific memory CD8 T cells with private specificity. Am. J. Transplant. 2010, 10, 1738–1748.
Morris, G.P.; Allen, P.M. Cutting edge: Highly alloreactive dual TCR T cells play a dominant role in graft-versus-host disease. J. Immunol. 2009, 182, 6639–6643.
Morris, G.P.; Uy, G.L.; Donermeyer, D.; Dipersio, J.F.; Allen, P.M. Dual receptor T cells mediate pathologic alloreactivity in patients with acute graft-versus-host disease. Sci. Transl. Med. 2013, 5, 188ra174.
Lask, A.; Goichberg, P.; Cohen, A.; Goren-Arbel, R.; Milstein, O.; Aviner, S.; Feine, I.; Ophir, E.; Reich-Zeliger, S.; Hagin, D.; et al. TCR-independent killing of B cell malignancies by anti-third-party CTLs: The critical role of MHC-CD8 engagement. J. Immunol. 2011, 187, 2006–2014.
Lask, A.; Ophir, E.; Or-Geva, N.; Cohen-Fredarow, A.; Afik, R.; Eidelstein, Y.; Reich-Zeliger, S.; Nathansohn, B.; Edinger, M.; Negrin, R.S.; et al. A new approach for eradication of residual lymphoma cells by host nonreactive anti-third-party central memory CD8 T cells. Blood 2013, 121, 3033–3040.
How to Cite
Alloreactive Cellular Strategies for Targeted Leukemia Immunotherapy Via Transient Donor Cell Engagement. (2025). Global Journal of Medical and Pharmaceutical Sciences, 4(05), 1-6. https://doi.org/10.55640/
Most read articles by the same author(s)
- B. Arun Babu, AUGMENTING WITHAFERIN-A'S ANTIPROLIFERATIVE POTENTIAL AGAINST EXPERIMENTAL HEPATOCELLULAR CARCINOMA , Global Journal of Medical and Pharmaceutical Sciences: Vol. 2 No. 07 (2023): Volume 02 Issue 07
- B. Vijay Babu, COMPARATIVE PHYSICOCHEMICAL EVALUATION OF ASHWAGANDHARISTA FORMULATIONS: TRADITIONAL VS. MODERN METHODS , Global Journal of Medical and Pharmaceutical Sciences: Vol. 2 No. 08 (2023): Volume 02 Issue 08
- Ali Ahmad Albagdady, Ahmad Alotaibi, ASSESSMENT OF PATIENT PREFERENCES FOR CLINICAL ATTIRE IN MILITARY HEALTHCARE FACILITIES: A STUD IN KUWAIT , Global Journal of Medical and Pharmaceutical Sciences: Vol. 2 No. 03 (2023): Volume 02 Issue 03
- Akshay Kallingal, REVOLUTIONIZING DRUG DELIVERY: CUBOSOMES NANOPARTICLES AT THE FOREFRONT , Global Journal of Medical and Pharmaceutical Sciences: Vol. 3 No. 01 (2024): Volume 03 Issue 01
- Ihaan Ahmad, DENTAL HEALTH INVESTIGATION: CORRELATING SALIVARY CALCIUM AND PHOSPHATE LEVELS WITH DENTAL CARIES IN SOFT DRINKS FACTORY WORKERS , Global Journal of Medical and Pharmaceutical Sciences: Vol. 3 No. 05 (2024): Volume 03 Issue 05
- Abdullahi Ebenezer, Samuel Adesewa, LASSA FEVER MITIGATION: COMBATTING AN EMERGING INFECTIOUS DISEASE THREAT , Global Journal of Medical and Pharmaceutical Sciences: Vol. 2 No. 04 (2023): Volume 02 Issue 04
- Ramadevi Pichandi, Suresh Reddy, EXPLORING HYPOTHYROID GOITRE DUE TO EXCESS IODINE AMONG SOUTH INDIANS , Global Journal of Medical and Pharmaceutical Sciences: Vol. 2 No. 12 (2023): Volume 02 Issue 12
- Ahmed Nawar, Zawawy Mokhtar, RADIOFREQUENCY VS. CRYOABLATION FOR PAROXYSMAL ATRIAL FIBRILLATION: A COMPREHENSIVE COMPARATIVE STUDY , Global Journal of Medical and Pharmaceutical Sciences: Vol. 1 No. 01 (2022): Volume 01 Issue 01
- Madhuri Pagariya, DEVELOPMENT AND ASSESSMENT OF SUSTAINED RELEASE SOLID DISPERSION OF GLIMEPIRIDE , Global Journal of Medical and Pharmaceutical Sciences: Vol. 3 No. 08 (2024): Volume 03 Issue 08
- Sushmita Das, TRANSDERMAL DRUG DELIVERY: INNOVATIONS, CHALLENGES, AND FUTURE DIRECTIONS , Global Journal of Medical and Pharmaceutical Sciences: Vol. 3 No. 09 (2024): Volume 03 Issue 09
Similar Articles
- Güray Saydam, Ahmet Emre Eşkazan, Birol Güvenç, Mehmet Sönmez, Selami Koçak Toprak, Mehtap Tatar, Burçin Kahveci Kaplan, Barış Uçar, Özlem Gür, İbrahim Haznedaroğlu, COST OF CHRONIC MYELOID LEUKEMIA FROM THE PAYER’S PERSPECTIVE IN TÜRKIYE: RESULTS OF A DELPHI PANEL ANALYSIS , Global Journal of Medical and Pharmaceutical Sciences: Vol. 3 No. 12 (2024): Volume 03 Issue 12
- Dr. Lina R. Haddad, Dr. Yasmin A. El-Zein, Thyroid Dysfunction in Pediatric Celiac Disease: A Cross-Sectional Study on the Prevalence and Clinical Implications of Screening , Global Journal of Medical and Pharmaceutical Sciences: Vol. 4 No. 08 (2025): Volume 04 Issue 08
- Dr. Farah Al-Mutairi, Prof. Samuel K. Boateng, Investigating the Impact of Glibenclamide, Catechin, and Azadirachta indica Leaf Extract on Pancreatic Beta Cell Regeneration in Alloxan-Induced Diabetic Rats , Global Journal of Medical and Pharmaceutical Sciences: Vol. 4 No. 09 (2025): Volume 04 Issue 09
- Abdullahi Ebenezer, Samuel Adesewa, LASSA FEVER MITIGATION: COMBATTING AN EMERGING INFECTIOUS DISEASE THREAT , Global Journal of Medical and Pharmaceutical Sciences: Vol. 2 No. 04 (2023): Volume 02 Issue 04
- Mahmoud Arafa, REVOLUTIONIZING ALVEOLAR CLEFT REPAIR: AUTOGENOUS BONE MARROW-DERIVED MESENCHYMAL STEM CELLS , Global Journal of Medical and Pharmaceutical Sciences: Vol. 2 No. 06 (2023): Volume 02 Issue 06
- Mehtap Tatar, Buket Öztürk, Deniz Aydoğan, Fatih Köse, Ender Dulundu, Şahin Laçin, Feyza Dilber, Mehmet Ali Şendur, Mesut Şeker, Karaca Mustafa, Sezer Sağlam, Birol Yıldız, Erdem Göker, Dane Faysal, Şuayıb Yalçın, Cost of Hepatocellular Carcinoma from the Payer’s Perspective in Türkiye: Results of a Delphi Panel Analysis , Global Journal of Medical and Pharmaceutical Sciences: Vol. 3 No. 09 (2024): Volume 03 Issue 09
- Leena Patidar, EVALUATING THE IMPACT OF PHARMACIST-LED PATIENT COUNSELLING ON QUALITY OF LIFE IN ASTHMA PATIENTS , Global Journal of Medical and Pharmaceutical Sciences: Vol. 3 No. 09 (2024): Volume 03 Issue 09
- Dr. Liana V. Petrov, Melatonin's Pro-Apoptotic Efficacy in Mitigating Postmenopausal Osteoporosis: A Mechanistic Investigation via the BMAL1/ROS/MAPK-p38 Signaling Axis in RAW264.7 Cells , Global Journal of Medical and Pharmaceutical Sciences: Vol. 4 No. 11 (2025): Volume 04 Issue 11
- Sana Ansari, Zineb Hassan, UNVEILING FOLLICULAR THYROID CARCINOMA: A CASE OF EXTENSIVE CHEST WALL METASTASIS , Global Journal of Medical and Pharmaceutical Sciences: Vol. 2 No. 01 (2023): Volume 02 Issue 01
- Mohamed Mostafa, Ekramy Nwidu, LIVER FUNCTION ABNORMALITIES AMONG SUBSTANCE ABUSERS: AN IN-DEPTH EXAMINATION , Global Journal of Medical and Pharmaceutical Sciences: Vol. 2 No. 10 (2023): Volume 02 Issue 10
1-10 of 17
Next
You may also start an advanced similarity search for this article.