Bio

Bio


Robbie Majzner is an Instructor in the Division of Pediatric Hematology-Oncology at the Stanford University School of Medicine. After graduating with a BA in computer science from Columbia University, Dr. Majzner attended Harvard Medical School where he developed an interest in pediatric oncology. He completed his residency training in pediatrics at New York Presbyterian-Columbia and fellowship training in pediatric hematology-oncology at Johns Hopkins and the National Cancer Institute. Through his research, he aims to bring advances in cell therapy to children with incurable cancers. Clinically, Dr. Majzner cares for patients with neuroblastoma and other solid tumors. He is board certified in pediatrics and pediatric hematology-oncology.

Clinical Focus


  • Cancer immunotherapy
  • Neuroblastoma
  • Cell therapy
  • Pediatric sarcomas
  • Solid tumors of childhood and adolescence
  • Pediatric oncology
  • Pediatric Hematology-Oncology

Academic Appointments


Honors & Awards


  • Young Investigator Award, American Society of Pediatric Hematology/Oncology (05/2018)
  • SARC Career Development Award, Sarcoma Alliance for Research through Collaboration (07/2017-07/2018)
  • Young Investigator Award, Hyundai Hope on Wheels (07/2018-07/2020)
  • AACR-AbbVie Scholar-in-Training Award, American Association for Cancer Research (04/2016)
  • Fellows Award for Research Excellence, National Institutes of Health - National Cancer Institute (06/2016)

Professional Education


  • Board Certification: Pediatric Hematology-Oncology, American Board of Pediatrics (2017)
  • Fellowship:Johns Hopkins and National Cancer Institute Ped Hematology and Oncology TrainingMD
  • Medical Education:Harvard Medical School (2009) MA
  • Residency:NY Presbyterian Hospital Columbia Pediatric Residency (2012) NY
  • Board Certification: Pediatrics, American Board of Pediatrics (2013)
  • American Board of Pediatrics, Pediatric Hematology-Oncology (2017)

Research & Scholarship

Clinical Trials


  • CD19/CD22 Chimeric Antigen Receptor T Cells and Chemotherapy in Treating Children or Young Adults With Recurrent or Refractory CD19 Positive B Acute Lymphoblastic Leukemia Recruiting

    This phase I trial studies the best dose and side effects of CD19/CD22 chimeric antigen receptor (CAR) T cells when given together with chemotherapy, and to see how well they work in treating children or young adults with CD19 positive B acute lymphoblastic leukemia that has come back or does not respond to treatment. A CAR is a genetically-engineered receptor made so that immune cells (T cells) can attack cancer cells by recognizing and responding to the CD19/CD22 proteins. These proteins are commonly found on B acute lymphoblastic leukemia. Drugs used in chemotherapy, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CD19/CD22-CAR T cells and chemotherapy may work better in treating children or young adults with B acute lymphoblastic leukemia.

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Publications

All Publications


  • Potent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M+ diffuse midline gliomas. Nature medicine Mount, C. W., Majzner, R. G., Sundaresh, S., Arnold, E. P., Kadapakkam, M., Haile, S., Labanieh, L., Hulleman, E., Woo, P. J., Rietberg, S. P., Vogel, H., Monje, M., Mackall, C. L. 2018

    Abstract

    Diffuse intrinsic pontine glioma (DIPG) and other diffuse midline gliomas (DMGs) with mutated histone H3 K27M (H3-K27M)1-5 are aggressive and universally fatal pediatric brain cancers 6 . Chimeric antigen receptor (CAR)-expressing T cells have mediated impressive clinical activity in B cell malignancies7-10, and recent results suggest benefit in central nervous system malignancies11-13. Here, we report that patient-derived H3-K27M-mutant glioma cell cultures exhibit uniform, high expression of the disialoganglioside GD2. Anti-GD2 CAR T cells incorporating a 4-1BBz costimulatory domain 14 demonstrated robust antigen-dependent cytokine generation and killing of DMG cells in vitro. In five independent patient-derived H3-K27M+ DMG orthotopic xenograft models, systemic administration of GD2-targeted CAR T cells cleared engrafted tumors except for a small number of residual GD2lo glioma cells. To date, GD2-targeted CAR T cells have been well tolerated in clinical trials15-17. Although GD2-targeted CAR T cell administration was tolerated in the majority of mice bearing orthotopic xenografts, peritumoral neuroinflammation during the acute phase of antitumor activity resulted in hydrocephalus that was lethal in a fraction of animals. Given the precarious neuroanatomical location of midline gliomas, careful monitoring and aggressive neurointensive care management will be required for human translation. With a cautious multidisciplinary clinical approach, GD2-targeted CAR T cell therapy for H3-K27M+ diffuse gliomas of pons, thalamus and spinal cord could prove transformative for these lethal childhood cancers.

    View details for DOI 10.1038/s41591-018-0006-x

    View details for PubMedID 29662203

  • Harnessing the Immunotherapy Revolution for the Treatment of Childhood Cancers CANCER CELL Majzner, R. G., Heitzeneder, S., Mackall, C. L. 2017; 31 (4): 476-485

    Abstract

    Cancer immunotherapies can be classified into agents that amplify natural immune responses (e.g., checkpoint inhibitors) versus synthetic immunotherapies designed to initiate new responses (e.g., monoclonal antibodies [mAbs], chimeric antigen receptors [CARs]). Checkpoint inhibitors mediate unprecedented benefit in some adult cancers, but have not demonstrated significant activity in pediatric cancers, likely due their paucity of neoantigens. In contrast, synthetic immunotherapies such as mAbs and CAR T cells demonstrate impressive effects against childhood cancers. Intense efforts are underway to enhance the effectiveness of pediatric cancer immunotherapies through improved engineering of synthetic immunotherapies and by combining these with agents designed to amplify immune responses.

    View details for DOI 10.1016/j.ccell.2017.03.002

    View details for Web of Science ID 000398670600005

    View details for PubMedID 28366678

  • Tumor Antigen and Receptor Densities Regulate Efficacy of a Chimeric Antigen Receptor Targeting Anaplastic Lymphoma Kinase. Molecular therapy : the journal of the American Society of Gene Therapy Walker, A. J., Majzner, R. G., Zhang, L., Wanhainen, K., Long, A. H., Nguyen, S. M., Lopomo, P., Vigny, M., Fry, T. J., Orentas, R. J., Mackall, C. L. 2017

    Abstract

    We explored the utility of targeting anaplastic lymphoma kinase (ALK), a cell surface receptor overexpressed on pediatric solid tumors, using chimeric antigen receptor (CAR)-based immunotherapy. T cells expressing a CAR incorporating the single-chain variable fragment sequence of the ALK48 mAb linked to a 4-1BB-CD3ζ signaling domain lysed ALK-expressing tumor lines and produced interferon-gamma upon antigen stimulation but had limited anti-tumor efficacy in two xenograft models of human neuroblastoma. Further exploration demonstrated that cytokine production was highly dependent upon ALK target density and that target density of ALK on neuroblastoma cell lines was insufficient for maximal activation of CAR T cells. In addition, ALK CAR T cells demonstrated rapid and complete antigen-induced loss of receptor from the T cell surface via internalization. Using a model that simultaneously modulated antigen density and CAR expression, we demonstrated that CAR functionality is regulated by target antigen and CAR density and that low expression of either contributes to limited anti-tumor efficacy of the ALK CAR. These data suggest that stoichiometric relationships between CAR receptors and target antigens may significantly impact the anti-tumor efficacy of CAR T cells and that manipulation of these parameters could allow precise tuning of CAR T cell activity.

    View details for DOI 10.1016/j.ymthe.2017.06.008

    View details for PubMedID 28676342

  • CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nature medicine Fry, T. J., Shah, N. N., Orentas, R. J., Stetler-Stevenson, M., Yuan, C. M., Ramakrishna, S., Wolters, P., Martin, S., Delbrook, C., Yates, B., Shalabi, H., Fountaine, T. J., Shern, J. F., Majzner, R. G., Stroncek, D. F., Sabatino, M., Feng, Y., Dimitrov, D. S., Zhang, L., Nguyen, S., Qin, H., Dropulic, B., Lee, D. W., Mackall, C. L. 2017

    Abstract

    Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent effects in relapsed and/or refractory pre-B cell acute lymphoblastic leukemia (B-ALL), but antigen loss is a frequent cause of resistance to CD19-targeted immunotherapy. CD22 is also expressed in most cases of B-ALL and is usually retained following CD19 loss. We report results from a phase 1 trial testing a new CD22-targeted CAR (CD22-CAR) in 21 children and adults, including 17 who were previously treated with CD19-directed immunotherapy. Dose-dependent antileukemic activity was observed, with complete remission obtained in 73% (11/15) of patients receiving ≥1 × 106 CD22-CAR T cells per kg body weight, including 5 of 5 patients with CD19dim or CD19- B-ALL. Median remission duration was 6 months. Relapses were associated with diminished CD22 site density that likely permitted CD22+ cell escape from killing by CD22-CAR T cells. These results are the first to establish the clinical activity of a CD22-CAR in B-ALL, including leukemia resistant to anti-CD19 immunotherapy, demonstrating potency against B-ALL comparable to that of CD19-CAR at biologically active doses. Our results also highlight the critical role played by antigen density in regulating CAR function.

    View details for DOI 10.1038/nm.4441

    View details for PubMedID 29155426

  • CAR T Cell Therapy for Neuroblastoma FRONTIERS IN IMMUNOLOGY Richards, R. M., Sotillo, E., Majzner, R. G. 2018; 9
  • Tumor Antigen Escape from CAR T-cell Therapy. Cancer discovery Majzner, R. G., Mackall, C. L. 2018

    Abstract

    Emerging data from chimeric antigen receptor (CAR) T-cell trials in B-cell malignancies demonstrate that a common mechanism of resistance to this novel class of therapeutics is the emergence of tumors with loss or downregulation of the target antigen. Antigen loss or antigen-low escape is likely to emerge as an even greater barrier to success in solid tumors, which manifest greater heterogeneity in target antigen expression. Potential approaches to overcome this challenge include engineering CAR T cells to achieve multispecificity and to respond to lower levels of target antigen and more efficient induction of natural antitumor immune responses as a result of CAR-induced inflammation. In this article, we review the evidence to date for antigen escape and downregulation and discuss approaches currently under study to overcome these obstacles.Significance: Antigen escape and downregulation have emerged as major issues impacting the durability of CAR T-cell therapy. Here, we explore their incidence and ways to overcome these obstacles in order to improve clinical outcomes. Cancer Discov; 8(10); 1-8. ©2018 AACR.

    View details for DOI 10.1158/2159-8290.CD-18-0442

    View details for PubMedID 30135176

  • ANTI-GD2 CHIMERIC ANTIGEN RECEPTOR T CELLS AS A POTENT IMMUNOTHERAPY REGIMEN IN XENOGRAFT MODELS OF HISTONE 3 K27M MUTANT DIFFUSE MIDLINE GLIOMA Mount, C., Majzner, R., Sundaresh, S., Arnold, E., Kadapakkam, M., Haile, S., Labanieh, L., Woo, P., Rietberg, S., Vogel, H., Monje, M., Mackall, C. OXFORD UNIV PRESS INC. 2018: 56
  • Programming CAR-T cells to kill cancer NATURE BIOMEDICAL ENGINEERING Labanieh, L., Majzner, R. G., Mackall, C. L. 2018; 2 (6): 377–91
  • CAR T CELLS TARGETING B7-H3, A PAN-CANCER ANTIGEN, DEMONSTRATE POTENT PRECLINICAL ACTIVITY AGAINST PEDIATRIC SOLID TUMORS AND BRAIN TUMORS Majzner, R., Nellan, A., Heitzeneder, S., Theruvath, J., Mackall, C. WILEY. 2018
  • B7-H3 CAR T CELLS MEDIATE IN VITRO AND IN VIVO ACTIVITY AGAINST NEUROBLASTOMA XENOGRAFTS Kadapakkam, M., Majzner, R., Xu, P., Mackall, C. WILEY. 2018
  • Neurotoxicity Associated with a High-Affinity GD2 CAR-Letter. Cancer immunology research Majzner, R. G., Weber, E. W., Lynn, R. C., Xu, P., Mackall, C. L. 2018; 6 (4): 494–95

    View details for DOI 10.1158/2326-6066.CIR-18-0089

    View details for PubMedID 29610423

  • Post-Transplantation Cyclophosphamide after Bone Marrow Transplantation Is Not Associated with an Increased Risk of Donor-Derived Malignancy BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Majzner, R. G., Mogri, H., Varadhan, R., Brown, P., Cooke, K. R., Bolanos-Meade, J., Swinnen, L., Kanakry, J., Luznik, L., Jones, R. J., Fuchs, E., Ambinder, R., Kasamon, Y., Symons, H. J. 2017; 23 (4): 612-617

    Abstract

    Post-transplantation cyclophosphamide (PTCy) can be used for graft-versus-host disease (GVHD) prophylaxis alone or in combination with other agents and is associated with excellent rates of engraftment and acute and chronic GVHD, as well as absence of post-transplantation lymphoproliferative disease. No study has previously evaluated the risk for developing donor-derived malignancy (DDM) in patients who receive PTCy. Giving chemotherapy in the immediate post-transplantation period carries with it a theoretic risk of disturbing the graft at a time of increased hematopoietic stress and causing or accelerating the development of malignancy. From 2000 to 2011, 789 patients underwent allogeneic transplantation and received PTCy at the Johns Hopkins Hospital. There were 4 cases of DDM identified among this large population, which is similar to or below the rate of DDM published in the literature. We found that the estimated cumulative incidence by competing risk analysis of DDM is 1.4% (SE, 1.02%). The use of PTCy does not appear to increase the risk of DDM.

    View details for DOI 10.1016/j.bbmt.2016.12.640

    View details for Web of Science ID 000397364300011

    View details for PubMedID 28062216

  • Assessment of programmed death-ligand 1 expression and tumor-associated immune cells in pediatric cancer tissues. Cancer Majzner, R. G., Simon, J. S., Grosso, J. F., Martinez, D., Pawel, B. R., Santi, M., Merchant, M. S., Geoerger, B., Hezam, I., Marty, V., Vielh, P., Daugaard, M., Sorensen, P. H., Mackall, C. L., Maris, J. M. 2017

    Abstract

    Programmed death 1 (PD-1) signaling in the tumor microenvironment dampens immune responses to cancer, and blocking this axis induces antitumor effects in several malignancies. Clinical studies of PD-1 blockade are only now being initiated in pediatric patients, and little is known regarding programmed death-ligand 1 (PD-L1) expression in common childhood cancers. The authors characterized PD-L1 expression and tumor-associated immune cells (TAICs) (lymphocytes and macrophages) in common pediatric cancers.Whole slide sections and tissue microarrays were evaluated by immunohistochemistry for PD-L1 expression and for the presence of TAICs. TAICs were also screened for PD-L1 expression.Thirty-nine of 451 evaluable tumors (9%) expressed PD-L1 in at least 1% of tumor cells. The highest frequency histotypes comprised Burkitt lymphoma (80%; 8 of 10 tumors), glioblastoma multiforme (36%; 5 of 14 tumors), and neuroblastoma (14%; 17 of 118 tumors). PD-L1 staining was associated with inferior survival among patients with neuroblastoma (P = .004). Seventy-four percent of tumors contained lymphocytes and/or macrophages. Macrophages were significantly more likely to be identified in PD-L1-positive versus PD-L1-negative tumors (P < .001).A subset of diagnostic pediatric cancers exhibit PD-L1 expression, whereas a much larger fraction demonstrates infiltration with tumor-associated lymphocytes. PD-L1 expression may be a biomarker for poor outcome in neuroblastoma. Further preclinical and clinical investigation will define the predictive nature of PD-L1 expression in childhood cancers both at diagnosis and after exposure to chemoradiotherapy. Cancer 2017. © 2017 American Cancer Society.

    View details for DOI 10.1002/cncr.30724

    View details for PubMedID 28608950

  • New developments in immunotherapy for pediatric solid tumors. Current opinion in pediatrics Schultz, L. M., Majzner, R., Davis, K. L., Mackall, C. 2017

    Abstract

    Building upon preclinical advances, we are uncovering immunotherapy strategies that are translating into improved outcomes in tumor subsets. Advanced pediatric solid tumors carry poor prognoses and resultant robust efforts to apply immunotherapy advances to pediatric solid tumors are in progress. Here, we discuss recent developments in the field using mAb and mAb-based therapies including checkpoint blockade and chimeric antigen receptors (CARs).The pediatric solid tumor mAb experience targeting the diganglioside, GD2, for patients with neuroblastoma has been the most compelling to date. GD2 and alternative antigen-specific mAbs are now being incorporated into antibody-drug conjugates, bispecific antibodies and CARs for treatment of solid tumors. CARs in pediatric solid tumors have not yet achieved comparative responses to the hematologic CAR experience; however, novel strategies such as bispecific targeting, intratumoral administration and improved understanding of T-cell biology may yield enhanced CAR-efficacy. Therapeutic effect using single-agent checkpoint blocking antibodies in pediatric solid tumors also remains limited to date. Combinatorial strategies continue to hold promise and the clinical effect in tumor subsets with high antigenic burden is being explored.Pediatric immunotherapy remains at early stages of translation, yet we anticipate that with advanced technology, we will achieve widespread, efficacious use of immunotherapy for pediatric solid tumors.

    View details for DOI 10.1097/MOP.0000000000000564

    View details for PubMedID 29189429

  • Pulmonary function after hematopoietic stem cell transplantation is significantly better in pediatric recipients following reduced toxicity compared with myeloablative conditioning BONE MARROW TRANSPLANTATION Majzner, R., Sandoval, C., Dozor, A. J., Jin, Z., Van de Ven, C., Dalal, R., Morris, E., Harrison, L., Wolownik, K., Fabricatore, S., Baxter-Lowe, L. A., Cairo, M. S. 2016; 51 (11): 1530-1532

    View details for DOI 10.1038/bmt.2016.172

    View details for Web of Science ID 000387243700025

    View details for PubMedID 27322849

  • T cell depletion utilizing CD34(+) stem cell selection and CD3(+) addback from unrelated adult donors in paediatric allogeneic stem cell transplantation recipients BRITISH JOURNAL OF HAEMATOLOGY Geyer, M. B., Ricci, A. M., Jacobson, J. S., Majzner, R., Duffy, D., van de Ven, C., Ayello, J., Bhatia, M., Garvin, J. H., George, D., Satwani, P., Harrison, L., Morris, E., Semidei-Pomales, M., Schwartz, J., Alobeid, B., Baxter-Lowe, L. A., Cairo, M. S. 2012; 157 (2): 205-219

    Abstract

    CD34-selected haploidentical and unrelated donor allogeneic stem cell transplantation (AlloSCT) in paediatric recipients is associated with sustained engraftment and low risk of acute graft-versus-host disease (aGVHD), but limited by delayed immune reconstitution and increased risk of viral and fungal infection. The optimal dose of donor T cells to prevent graft failure and minimize risk of early opportunistic infection and post-transplant lymphoproliferative disorder (PTLD), while avoiding severe aGVHD, remains unknown. We prospectively studied CD34-selected 8-10/10 human leucocyte antigen (HLA)-matched unrelated donor (MUD) peripheral blood stem cell transplantation (PBSCT) in a cohort of 19 paediatric AlloSCT recipients with malignant (n = 13) or non-malignant (n = 6) diseases. T cells were added back to achieve total dose 1·0-2·5 × 10(5)  CD3(+) /kg. GVHD pharmacoprophylaxis consisted only of tacrolimus. All patients engrafted neutrophils. Probabilities of grade II-IV aGVHD, limited chronic GVHD (cGVHD), and extensive cGVHD were 15·8%, 23·3%, and 0%, respectively. One patient developed PTLD. One-year infection-related mortality was 5·6%. T cell immune reconstitution was delayed. One-year overall survival was 82·3%. Five patients with malignant disease ultimately died from progressive disease. CD34-selected MUD PBSCT using a defined dose of T cell add-back resulted in high rates of engraftment and low risk of grade II-IV aGVHD, early transplantation-related mortality, and extensive cGVHD.

    View details for DOI 10.1111/j.1365-2141.2012.09048.x

    View details for Web of Science ID 000302062800009

    View details for PubMedID 22313507