The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Teclistamab is an active T cell–redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma
Open accessAbstract
B-cell maturation antigen (BCMA), a member of the tumor necrosis factor family of receptors, is predominantly expressed on the surface of terminally differentiated B cells. BCMA is highly expressed on plasmablasts and plasma cells from multiple myeloma (MM) patient samples. We developed a BCMAxCD3 bispecific antibody (teclistamab [JNJ-64007957]) to recruit and activate T cells to kill BCMA-expressing MM cells. Teclistamab induced cytotoxicity of BCMA+ MM cell lines in vitro (H929 cells, 50% effective concentration [EC50] = 0.15 nM; MM.1R cells, EC50 = 0.06 nM; RPMI 8226 cells, EC50 = 0.45 nM) with concomitant T-cell activation (H929 cells, EC50 = 0.21 nM; MM.1R cells, EC50 = 0.1 nM; RPMI 8226 cells, EC50 = 0.28 nM) and cytokine release. This activity was further increased in the presence of a γ-secretase inhibitor (LY-411575). Teclistamab also depleted BCMA+ cells in bone marrow samples from MM patients in an ex vivo assay with an average EC50 value of 1.7 nM. Under more physiological conditions using healthy human whole blood, teclistamab mediated dose-dependent lysis of H929 cells and activation of T cells. Antitumor activity of teclistamab was also observed in 2 BCMA+ MM murine xenograft models inoculated with human T cells (tumor inhibition with H929 model and tumor regression with the RPMI 8226 model) compared with vehicle and antibody controls. The specific and potent activity of teclistamab against BCMA-expressing cells from MM cell lines, patient samples, and MM xenograft models warrant further evaluation of this bispecific antibody for the treatment of MM. Phase 1 clinical trials (monotherapy, #NCT03145181; combination therapy, #NCT04108195) are ongoing for patients with relapsed/refractory MM.
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“This effect occurs regardless of T-cell–receptor specificity or major histocompatibility complex class I molecules on the surface of myeloma cells.18”
From Teclistamab in Relapsed or Refractory Multiple Myeloma (2022) · cites this paper as [18]
In the citing paper
“Teclistamab redirects CD3+ T cells to BCMA+ myeloma cells, resulting in T-cell activation and subsequent lysis and death of BCMA+ cells.18”
From Teclistamab in Relapsed or Refractory Multiple Myeloma (2022) · cites this paper as [18]
Citations
Cites
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International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma
Rajkumar, S. V., Dimopoulos, M. A., Palumbo, A., Blade, J., Merlini, G., Mateos, M.-V., Kumar, S., Hillengass, J., Kastritis, E., Richardson, P., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70442-5 · Cited by 4,978 · cited 1×
“MM is characterized by overproduction of M protein, which can lead to bone lesions, increased susceptibility to infections, anemia, hypercalcemia, and renal insufficiency.(2) Within the past decade, the introduction of proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies has changed the landscape o…”
BackgroundPalumbo, A. P., & Anderson, K. C. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1011442 · Cited by 2,382 · cited 1×
“Multiple myeloma (MM) is a malignant plasma cell disorder that leads to clonal proliferation of terminally differentiated plasma cells in the bone marrow (BM) and accounts for ;10% of all hematologic cancers.(1) MM is characterized by overproduction of M protein, which can lead to bone lesions, increased susceptibilit…”
BackgroundRaje, N. S., & Anderson, K. C. (2000) · Current Treatment Options in Oncology · doi:10.1007/s11864-000-0017-x · Cited by 2,164
Bortezomib plus Melphalan and Prednisone for Initial Treatment of Multiple Myeloma
San Miguel, J. F., Schlag, R., Khuageva, N. K., Dimopoulos, M. A., Shpilberg, O., Kropff, M., Spicka, I., Petrucci, M. T., Palumbo, A., Samoilova, O. S., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0801479 · Cited by 1,899
Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma.
Raje, N., Berdeja, J., Lin, Y., Siegel, D., Jagannath, S., Madduri, D., Liedtke, M., Rosenblatt, J., Maus, M. V., Turka, A., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1817226 · Cited by 1,730 · cited 1×
“Therapeutic approaches such as chimeric antigen receptor T-cell therapies and bispecific T-cell engagers that use T cell–mediated cytotoxicity to target BCMA on plasma cells have shown deep responses in patients with relapsed or refractory disease.(21-25) Another class of T-cell redirecting therapy in development for…”
BackgroundElotuzumab Therapy for Relapsed or Refractory Multiple Myeloma
Lonial, S., Dimopoulos, M., Palumbo, A., White, D., Grosicki, S., Spicka, I., Walter-Croneck, A., Moreau, P., Mateos, M.-V., Magen, H., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1505654 · Cited by 1,322
TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease
Gross, J. A., Johnston, J. V., Mudri, S., Enselman, R., Dillon, S. R., Madden, K., Xu, W., Parrish-Novak, J. E., Foster, D., Lofton-Day, C., et al. (2000) · Nature · doi:10.1038/35010115 · Cited by 1,175 · cited 2×
“Upon binding to its ligands, a proliferation-inducing ligand (APRIL; CD256) and BAFF (CD257), BCMA activates p38/NF-kB and induces upregulation of antiapoptotic proteins to regulate B-cell maturation, proliferation, and survival.(16-20) Increased levels of a soluble form of BCMA (sBCMA), produced through cleavage at t…”
BackgroundTargeting CD38 with Daratumumab Monotherapy in Multiple Myeloma
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“Within the past decade, the introduction of proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies has changed the landscape of myeloma management, leading to improved disease control and prolonged survival.(3-12) Despite these therapeutic advances, nearly all patients will eventually relapse”
BackgroundRichardson, P. G., Weller, E., Lonial, S., Jakubowiak, A. J., Jagannath, S., Raje, N. S., Avigan, D. E., Xie, W., Ghobrial, I. M., Schlossman, R. L., et al. (2010) · Blood · doi:10.1182/blood-2010-02-268862 · Cited by 861 · cited 1×
“Within the past decade, the introduction of proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies has changed the landscape of myeloma management, leading to improved disease control and prolonged survival.(3-12) Despite these therapeutic advances, nearly all patients will eventually relapse”
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Sorted by citations
Teclistamab in Relapsed or Refractory Multiple Myeloma
Moreau, P., Garfall, A. L., van de Donk, N. W. C. J., Nahi, H., San-Miguel, J. F., Oriol, A., Nooka, A. K., Martin, T., Rosinol, L., Chari, A., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2203478 · Cited by 1,269
Emerging new therapeutic antibody derivatives for cancer treatment
Jin, S., Sun, Y., Xiao, L., Gu, X., Ning, J., Xu, Y., Chen, S., & Pan, L. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00868-x · Cited by 480
Usmani, S. Z., Garfall, A. L., van de Donk, N. W. C. J., Nahi, H., Miguel, J. F. S., Oriol, A., Rosiñol, L., Chari, A., Bhutani, M., Karlin, L., et al. (2021) · The Lancet · doi:10.1016/s0140-6736(21)01338-6 · Cited by 344
Self-citationFriedrich, M., Neri, P., Kehl, N., Michel, J., Steiger, S., Kilian, M., Leblay, N., Maity, R., Sankowski, R., Lee, H., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.008 · Cited by 289
The landscape of bispecific T cell engager in cancer treatment
Zhou, S., Liu, M., Ren, F., Meng, X., & Yu, J. (2021) · Biomarker Research · doi:10.1186/s40364-021-00294-9 · Cited by 240
“Teclistamab [60], REGN5458 [61], CC-93269 [62] PF-06863135 [63], and TNB-383B”
Metadata
- Authors
- Pillarisetti, K., Powers, G., Luistro, L., Babich, A., Baldwin, E., Li, Y., Zhang, X., Mendonça, M., Majewski, N., Nanjunda, R., Chin, D., Packman, K., Elsayed, Y., Attar, R., & Gaudet, F.
- Affiliations
- Oncology and
- Janssen Research & Development (United States) (US)
- IBM (United States) (US)
- Legend Biotech (United States) (US)
- Century Therapeutics (United States) (US)
- Venue
- Blood Advances
- Publisher
- American Society of Hematology
- Published
- 2020-09-21
- Volume
- 4
- Issue
- 18
- Pages
- 4538-4549
- ISSN
- 2473-9529 (ISSN-L)
- 2473-9537
- PMC
- PMC7509877
- OpenAlex
- W3087111554
- Cited by
- 144
- References
- 40
- Citations by year
- 2026: 23 · 2025: 21 · 2024: 31 · 2023: 27 · 2022: 19 · 2021: 20 · 2020: 1
- FWCI
- 10.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Blood Advances (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Keywords
- teclistamab, BCMA, multiple myeloma, bispecific antibodies, T cell redirection, T cell activation, gamma-secretase inhibitors, tumor cell lysis, xenograft models, relapsed/refractory multiple myeloma
- MeSH terms
- Animals, Humans, Lymphocyte Activation, Multiple Myeloma, T-Lymphocytes, Antibodies, Bispecific, Mice, B-Cell Maturation Antigen
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