Bio


Dr. Anne Marijn Kramer, MD, PhD, is a postdoctoral research fellow in the Division of Blood and Marrow Transplantation and Cellular Therapy at Stanford University. Dr. Kramer received her medical degree (with honors) from Amsterdam University in 2013. She conducted her PhD studies at University College London, studying binding kinetics of Chimeric Antigen Receptor (CAR) T cells. Her research at Stanford University focuses on developing methods to identify patients who are at high risk for relapse or developing side-effects after receiving CAR T therapy and to understand why these relapses and side-effects occur.

Honors & Awards


  • ASH abstract achievement award, American Society of Hematology (12/09/2023)
  • EHA Junior Research Grant, European Hematology Association (09/01/2022)
  • Paul Fentener van Vlissingen Fellowship, Lymph&Co (09/01/2022)
  • Prins Bernhard Cultuurfondsbeurs, Prins Bernhard Cultuurfonds (06/01/2013)
  • VSBfonds beurs, VSBfonds (06/01/2013)
  • NIHR GOSH/UCL ICH BRC PhD Scholarship, NIHR Great Ormond Street Hospital/UCL Institute of Child Health Biomedical Research Centre (04/01/2014)
  • CCA grant co-applicant, Cancer Center Amsterdam (03/01/2020)

Boards, Advisory Committees, Professional Organizations


  • President, Dutch Junior Society of Internal Medicine (2020 - 2021)
  • Board Member, Dutch Society of Internal Medicine (2020 - 2021)

Professional Education


  • Doctor of Medicine, University of Amsterdam (2013)
  • Doctorandus, University of Amsterdam (2011)
  • Diploma, Stedelijk Gymnasium Johan van Oldenbarnevelt (2005)
  • Doctor of Philosophy, University College London (2017)
  • PhD, University College London, Cancer Immunotherapy (2017)
  • MD, University of Amsterdam, Medicine (2013)

Stanford Advisors


Patents


  • Kramer AM, Kokalaki E, Pule MA. "United KingdomOff-rate CAR", UCLB, Sep 1, 2016
  • Mekkaoui L, Kramer AM, Ghorashian S, Pule MA. "United KingdomA CAR against CD19 based on a novel binder", UCLB, Mar 1, 2015

All Publications


  • A Phase 1 Clinical Trial of NKTR-255 with CD19-22 CAR-T Cell Therapy for Refractory B-cell Acute Lymphoblastic Leukemia. Blood Srinagesh, H. K., Jackson, C., Shiraz, P., Jeyakumar, N., Hamilton, M. P., Egeler, E., Mavroukakis, S., Kuo, A., Cancilla, J., Sahaf, B., Agarwal, N., Kanegai, A. M., Kramer, A. M., Arai, S., Bharadwaj, S., Dahiya, S., Hosoya, H., Johnston, L. J., Kennedy, V. E., Liedtke, M., Lowsky, R., Mikkilineni, L., Negrin, R. S., Rezvani, A. R., Sidana, S., Shizuru, J. A., Smith, M., Weng, W. K., Feldman, S. A., Frank, M. J., Lee, Z., Tagliaferri, M., Marcondes, A. M., Miklos, D. B., Mackall, C. L., Muffly, L. 2024

    Abstract

    While chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of B-cell malignancies, many patients relapse and therefore strategies to improve antitumor immunity are needed. We previously designed a novel autologous bispecific CAR targeting CD19 and CD22 (CAR19-22), which was well tolerated and associated with high response rates but relapse was common. Interleukin-15 (IL15) induces proliferation of diverse immune cells and can augment lymphocyte trafficking. Here, we report the results of a phase 1 clinical trial of the first combination of a novel recombinant polymer-conjugated IL15 receptor agonist (NKTR-255), with CAR19-22, in adults with relapsed / refractory B-cell acute lymphoblastic leukemia. Eleven patients were enrolled, nine of whom successfully received CAR19-22 followed by NKTR-255. There were no dose limiting toxicities, with transient fever and myelosuppression as the most common possibly related toxicities. We observed favorable efficacy with eight out of nine patients (89%) achieving measurable residual disease negative remission. At 12 months, progression-free survival for NKTR-255 was double that of historical controls (67% vs 38%). We performed correlative analyses to investigate the effects of IL15 receptor agonism. Cytokine profiling showed significant increases in IL15 and the chemokines CXCL9 and CXCL10. The increase in chemokines was associated with decreases in absolute lymphocyte counts and CD8+ CAR T-cells in blood and ten-fold increases in CSF CAR-T cells, suggesting lymphocyte trafficking to tissue. Combining NKTR-255 with CAR19-22 was safe, feasible and associated with high rates of durable responses (NCT03233854).

    View details for DOI 10.1182/blood.2024024952

    View details for PubMedID 38968138

  • CD22 CAR T cells demonstrate high response rates and safety in pediatric and adult B-ALL: Phase 1b results. Leukemia Schultz, L. M., Jeyakumar, N., Kramer, A. M., Sahaf, B., Srinagesh, H., Shiraz, P., Agarwal, N., Hamilton, M., Erickson, C., Jacobs, A., Moon, J., Baggott, C., Arai, S., Bharadwaj, S., Johnston, L. J., Liedtke, M., Lowsky, R., Meyer, E., Negrin, R., Rezvani, A., Shizuru, J., Sidana, S., Egeler, E., Mavroukakis, S., Tunuguntla, R., Gkitsas-Long, N., Retherford, A., Brown, A. K., Gramstrap-Petersen, A. L., IbaƱez, R. M., Feldman, S. A., Miklos, D. B., Mackall, C. L., Davis, K. L., Frank, M., Ramakrishna, S., Muffly, L. 2024

    Abstract

    Chimeric antigen receptor (CAR) T cells targeting CD22 (CD22-CAR) provide a therapeutic option for patients with CD22+ malignancies with progression after CD19-directed therapies. Using on-site, automated, closed-loop manufacturing, we conducted parallel Phase 1b clinical trials investigating a humanized CD22-CAR with 41BB costimulatory domain in children and adults with heavily treated, relapsed/refractory (r/r) B-ALL. Of 19 patients enrolled, 18 had successful CD22-CAR manufacturing, and 16 patients were infused. High grade (3-4) cytokine release syndrome (CRS) and immune effector-cell-associated neurotoxicity syndrome (ICANS) each occurred in only one patient; however, three patients experienced immune-effector-cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS). Twelve of 16 patients (75%) achieved CR with an overall 56% MRD-negative CR rate. Duration of response was overall limited (median 77 days), and CD22 expression was downregulated in 4/12 (33%) available samples at relapse. In summary, we demonstrate that closed-loop manufacturing of CD22-CAR T cells is feasible and is associated with a favorable safety profile and high CR rates in pediatric and adult r/r B-ALL, a cohort with limited CD22-CAR reporting.

    View details for DOI 10.1038/s41375-024-02220-y

    View details for PubMedID 38491306

    View details for PubMedCentralID 4993814

  • Transcriptional Profiling Associated with CD22 CAR T Cell Clinical Response in LBCL Kramer, A., Hamilton, M. P., Prabhu, S., Desai, M., Kuo, A., Ehlinger, Z., Agarwal, N., Su, Y., Gkitsas, N., Fowler, C., Keerthi, V., Retherford, A., Klysz, D., Tunuguntla, R., Feldman, S., Sahaf, B., Baird, J. H., Muffly, L. S., Mackall, C. L., Miklos, D. B., Good, Z., Frank, M. J. AMER SOC HEMATOLOGY. 2023
  • Manufacturing of a Subsequent Autologous CAR-T Product after Prior CAR-T Is Safe and Feasible Su, Y., Kramer, A., Hamilton, M. P., Agarwal, N., Feldman, S., Sahaf, B., Kuo, A., Mackall, C. L., Muffly, L. S., Miklos, D. B., Frank, M. J. AMER SOC HEMATOLOGY. 2023
  • CD22 CAR T Cell-Related IEC-HS Is Associated with an IFN-. Cytokine Signature Srinagesh, H., Baird, J. H., Agarwal, N., Su, Y., Kramer, A., Reschke, A., Jeyakumar, N., Bharadwaj, S., Schultz, L., Ramakrishna, S., Davis, K. L., Sahaf, B., Feldman, S., Mackall, C. L., Miklos, D. B., Muffly, L. S., Frank, M. J. AMER SOC HEMATOLOGY. 2023