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1. Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy

Author

Wienke, Judith, Visser, Lindy L., Kholosy, Waleed M., Keller, Kaylee M., Barisa, Marta, Poon, Evon, Munnings-Tomes, Sophie, Himsworth, Courtney, Calton, Elizabeth, Rodriguez, Ana, Bernardi, Ronald, van den Ham, Femke, van Hooff, Sander R., Matser, Yvette A.H., Tas, Michelle L., Langenberg, Karin P.S., Lijnzaad, Philip, Borst, Anne L., Zappa, Elisa, Bergsma, Francisca J., Strijker, Josephine G.M., Verhoeven, Bronte M., Mei, Shenglin, Kramdi, Amira, Restuadi, Restuadi, Sanchez-Bernabeu, Alvaro, Cornel, Annelisa M., Holstege, Frank C.P., Gray, Juliet C., Tytgat, Godelieve A.M., Scheijde-Vermeulen, Marijn A., Wijnen, Marc H.W.A., Dierselhuis, Miranda P., Straathof, Karin, Behjati, Sam, Wu, Wei, Heck, Albert J.R., Koster, Jan, Nierkens, Stefan, Janoueix-Lerosey, Isabelle, de Krijger, Ronald R., Baryawno, Ninib, Chesler, Louis, Anderson, John, Caron, Hubert N., Margaritis, Thanasis, van Noesel, Max M., and Molenaar, Jan J.

Published
2024
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2. Payload-delivering engineered γδ T cells display enhanced cytotoxicity, persistence, and efficacy in preclinical models of osteosarcoma

Author

Fowler, Daniel, primary, Barisa, Marta, additional, Southern, Alba, additional, Nattress, Callum, additional, Hawkins, Elizabeth, additional, Vassalou, Eleni, additional, Kanouta, Angeliki, additional, Counsell, John, additional, Rota, Enrique, additional, Vlckova, Petra, additional, Draper, Benjamin, additional, De Mooij, Tessa, additional, Farkas, Andrea, additional, Brezovjakova, Helena, additional, Baker, Alfie T., additional, Scotlandi, Katia, additional, Manara, Maria C., additional, Tape, Chris, additional, Chester, Kerry, additional, Anderson, John, additional, and Fisher, Jonathan, additional

Published
2024
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3. Blocking MIF secretion enhances CAR T-cell efficacy against neuroblastoma

Author

Strijker, Josephine G. M., primary, Pascual-Pasto, Guillem, additional, Kalmeijer, Yannine J., additional, Kalaitsidou, Elisavet, additional, Zhao, Chunlong, additional, McIntyre, Brendan, additional, Matlaga, Stephanie, additional, Visser, Lindy L., additional, Barisa, Marta, additional, Himsworth, Courtney, additional, Shah, Rivani, additional, Muller, Henrike, additional, Schild, Linda G., additional, Hains, Peter G., additional, Zhong, Qing, additional, Reddel, Roger, additional, Robinson, Phillip J., additional, Catena, Xavier, additional, Soengas, María S., additional, Margaritis, Thanasis, additional, Dekker, Frank J., additional, Anderson, John, additional, Molenaar, Jan J., additional, Bosse, Kristopher R., additional, Wu, Wei, additional, and Wienke, Judith, additional

Published
2024
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4. Functional avidity of anti-B7H3 CAR-T constructs predicts antigen density thresholds for triggering effector function

Author

Barisa, Marta, primary, Zappa, Elisa, additional, Muller, Henrike, additional, Shah, Rivani, additional, Buhl, Juliane, additional, Draper, Benjamin, additional, Himsworth, Courtney, additional, Bowers, Chantelle, additional, Munnings-Tomes, Sophie, additional, Nicolaidou, Marilena, additional, Morlando, Sonia, additional, Birley, Katie, additional, Leboreiro-Babe, Clara, additional, Vitali, Alice, additional, Privitera, Laura, additional, O’Sullivan, Kyle, additional, Greppi, Ailsa, additional, Buschhaus, Magdalena, additional, Román, Mario Barrera, additional, de Blank, Sam, additional, van den Ham, Femke, additional, van ‘t Veld, Brenna R., additional, Ferry, Gabrielle, additional, Donovan, Laura K., additional, Chesler, Louis, additional, Molenaar, Jan, additional, Drost, Jarno, additional, Rios, Anne, additional, Chester, Kerry, additional, Wienke, Judith, additional, and Anderson, John, additional

Published
2024
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5. Human peripheral γδT cell phenotypic and functional shift in response to stimulation with E.coli

Author

Barisa, Marta, Gustafsson, K. G., Anderson, J. A., and Bajaj-Elliott, M. B. E.

Subjects
618.92
Abstract

It is known that γδT cells provide immune-surveillance and host defense against infection and cancer. Our understanding of γδT cell functionality and antimicrobial immunity, however, remains poor. Limited data suggests that γδT cells can phagocytose particles and act as professional antigen-presenting cells (pAPCs). In order to examine γδT cell bacterial interactions, an ex vivo co-culture model of human peripheral blood mononuclear cell (PBMC) responses to Escherichia coli was employed. Following PBMC stimulation with E.coli, Vγ9Vδ2 cells underwent rapid T cell receptor (TCR)-dependent proliferation and functional transition from cytotoxic, inflammatory cytokine immunity, to cell expansion with diminished cytokine but increased costimulatory molecule expression, and capacity for professional phagocytosis. Phagocytosis was augmented by IgG opsonization, and inhibited by TCR-blockade, suggesting a licensing interaction involving the TCR and FcγR. Vγ9Vδ2 cells displayed potent cytotoxicity through TCR-dependent and independent mechanisms. Vγ9Vδ2 cell cytokine responses and cytotoxicity further presented with variable sensitivity to blocking of host butyrophilin 3A (BTN3A), in response to both, self and non-self, stimuli. We conclude that i) Vγ9Vδ2 T cells transition from early inflammatory cytotoxic killers to myeloid-like pAPCs in response to infectious stimuli, and that ii) Vγ9Vδ2 T cell recognition of targets is predominantly governed by TCR recognition of self stress markers in a BTN3A-dependent manner.

Published
2017

7. Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy

Author

Afd Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Afd Pharmaceutics, Biomolecular Mass Spectrometry and Proteomics, Pharmaceutics, Wienke, Judith, Visser, Lindy L, Kholosy, Waleed M, Keller, Kaylee M, Barisa, Marta, Poon, Evon, Munnings-Tomes, Sophie, Himsworth, Courtney, Calton, Elizabeth, Rodriguez, Ana, Bernardi, Ronald, van den Ham, Femke, van Hooff, Sander R, Matser, Yvette A H, Tas, Michelle L, Langenberg, Karin P S, Lijnzaad, Philip, Borst, Anne L, Zappa, Elisa, Bergsma, Francisca J, Strijker, Josephine G M, Verhoeven, Bronte M, Mei, Shenglin, Kramdi, Amira, Restuadi, Restuadi, Sanchez-Bernabeu, Alvaro, Cornel, Annelisa M, Holstege, Frank C P, Gray, Juliet C, Tytgat, Godelieve A M, Scheijde-Vermeulen, Marijn A, Wijnen, Marc H W A, Dierselhuis, Miranda P, Straathof, Karin, Behjati, Sam, Wu, Wei, Heck, Albert J R, Koster, Jan, Nierkens, Stefan, Janoueix-Lerosey, Isabelle, de Krijger, Ronald R, Baryawno, Ninib, Chesler, Louis, Anderson, John, Caron, Hubert N, Margaritis, Thanasis, van Noesel, Max M, Molenaar, Jan J, Afd Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Afd Pharmaceutics, Biomolecular Mass Spectrometry and Proteomics, Pharmaceutics, Wienke, Judith, Visser, Lindy L, Kholosy, Waleed M, Keller, Kaylee M, Barisa, Marta, Poon, Evon, Munnings-Tomes, Sophie, Himsworth, Courtney, Calton, Elizabeth, Rodriguez, Ana, Bernardi, Ronald, van den Ham, Femke, van Hooff, Sander R, Matser, Yvette A H, Tas, Michelle L, Langenberg, Karin P S, Lijnzaad, Philip, Borst, Anne L, Zappa, Elisa, Bergsma, Francisca J, Strijker, Josephine G M, Verhoeven, Bronte M, Mei, Shenglin, Kramdi, Amira, Restuadi, Restuadi, Sanchez-Bernabeu, Alvaro, Cornel, Annelisa M, Holstege, Frank C P, Gray, Juliet C, Tytgat, Godelieve A M, Scheijde-Vermeulen, Marijn A, Wijnen, Marc H W A, Dierselhuis, Miranda P, Straathof, Karin, Behjati, Sam, Wu, Wei, Heck, Albert J R, Koster, Jan, Nierkens, Stefan, Janoueix-Lerosey, Isabelle, de Krijger, Ronald R, Baryawno, Ninib, Chesler, Louis, Anderson, John, Caron, Hubert N, Margaritis, Thanasis, van Noesel, Max M, and Molenaar, Jan J

Published
2024

8. Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy

Author

CTI Nierkens, Cancer, Infection & Immunity, CTI Research, Pathologie Pathologen staf, Onderzoek Beeld, Wienke, Judith, Visser, Lindy L, Kholosy, Waleed M, Keller, Kaylee M, Barisa, Marta, Poon, Evon, Munnings-Tomes, Sophie, Himsworth, Courtney, Calton, Elizabeth, Rodriguez, Ana, Bernardi, Ronald, van den Ham, Femke, van Hooff, Sander R, Matser, Yvette A H, Tas, Michelle L, Langenberg, Karin P S, Lijnzaad, Philip, Borst, Anne L, Zappa, Elisa, Bergsma, Francisca J, Strijker, Josephine G M, Verhoeven, Bronte M, Mei, Shenglin, Kramdi, Amira, Restuadi, Restuadi, Sanchez-Bernabeu, Alvaro, Cornel, Annelisa M, Holstege, Frank C P, Gray, Juliet C, Tytgat, Godelieve A M, Scheijde-Vermeulen, Marijn A, Wijnen, Marc H W A, Dierselhuis, Miranda P, Straathof, Karin, Behjati, Sam, Wu, Wei, Heck, Albert J R, Koster, Jan, Nierkens, Stefan, Janoueix-Lerosey, Isabelle, de Krijger, Ronald R, Baryawno, Ninib, Chesler, Louis, Anderson, John, Caron, Hubert N, Margaritis, Thanasis, van Noesel, Max M, Molenaar, Jan J, CTI Nierkens, Cancer, Infection & Immunity, CTI Research, Pathologie Pathologen staf, Onderzoek Beeld, Wienke, Judith, Visser, Lindy L, Kholosy, Waleed M, Keller, Kaylee M, Barisa, Marta, Poon, Evon, Munnings-Tomes, Sophie, Himsworth, Courtney, Calton, Elizabeth, Rodriguez, Ana, Bernardi, Ronald, van den Ham, Femke, van Hooff, Sander R, Matser, Yvette A H, Tas, Michelle L, Langenberg, Karin P S, Lijnzaad, Philip, Borst, Anne L, Zappa, Elisa, Bergsma, Francisca J, Strijker, Josephine G M, Verhoeven, Bronte M, Mei, Shenglin, Kramdi, Amira, Restuadi, Restuadi, Sanchez-Bernabeu, Alvaro, Cornel, Annelisa M, Holstege, Frank C P, Gray, Juliet C, Tytgat, Godelieve A M, Scheijde-Vermeulen, Marijn A, Wijnen, Marc H W A, Dierselhuis, Miranda P, Straathof, Karin, Behjati, Sam, Wu, Wei, Heck, Albert J R, Koster, Jan, Nierkens, Stefan, Janoueix-Lerosey, Isabelle, de Krijger, Ronald R, Baryawno, Ninib, Chesler, Louis, Anderson, John, Caron, Hubert N, Margaritis, Thanasis, van Noesel, Max M, and Molenaar, Jan J

Published
2024

13. Editorial: Optimized gene-engineering and combination therapies to boost γδT cell immunotherapeutic performance.

Author

Barisa, Marta, Abate-Daga, Daniel, and Fisher, Jonathan

Subjects
ONCOLOGY, CYTOTOXIC T cells, GRAFT versus host disease
Abstract

This editorial explores the potential of gdT cell immunotherapy in cancer treatment. It discusses the limitations of traditional gene-modified abT cell therapies and highlights the unique features of gdT cells, such as their expression of TCRg/d and ability to cross-present antigens. The article covers topics like clinical trials, combination therapies, and methods of gdT cell product manufacture. It also mentions the importance of immune checkpoint blockade and the potential for combining gdT cells with other therapeutic approaches. The authors conclude by emphasizing the need for further research and clinical trials in this field. [Extracted from the article]

Published
2024
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14. Figure 2 from Shortwave Infrared Imaging Enables High-Contrast Fluorescence-Guided Surgery in Neuroblastoma

Author

Privitera, Laura, primary, Waterhouse, Dale J., primary, Preziosi, Alessandra, primary, Paraboschi, Irene, primary, Ogunlade, Olumide, primary, Da Pieve, Chiara, primary, Barisa, Marta, primary, Ogunbiyi, Olumide, primary, Weitsman, Gregory, primary, Hutchinson, J. Ciaran, primary, Cross, Kate, primary, Biassoni, Lorenzo, primary, Stoyanov, Danail, primary, Sebire, Neil, primary, Beard, Paul, primary, De Coppi, Paolo, primary, Kramer-Marek, Gabriela, primary, Anderson, John, primary, and Giuliani, Stefano, primary

Published
2023
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15. Data from Shortwave Infrared Imaging Enables High-Contrast Fluorescence-Guided Surgery in Neuroblastoma

Author

Privitera, Laura, primary, Waterhouse, Dale J., primary, Preziosi, Alessandra, primary, Paraboschi, Irene, primary, Ogunlade, Olumide, primary, Da Pieve, Chiara, primary, Barisa, Marta, primary, Ogunbiyi, Olumide, primary, Weitsman, Gregory, primary, Hutchinson, J. Ciaran, primary, Cross, Kate, primary, Biassoni, Lorenzo, primary, Stoyanov, Danail, primary, Sebire, Neil, primary, Beard, Paul, primary, De Coppi, Paolo, primary, Kramer-Marek, Gabriela, primary, Anderson, John, primary, and Giuliani, Stefano, primary

Published
2023
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16. Short-wave infrared imaging enables high-contrast fluorescence-guided surgery in neuroblastoma

Author

Privitera, Laura, primary, Waterhouse, Dale J., additional, Preziosi, Alessandra, additional, Paraboschi, Irene, additional, Ogunlade, Olumide, additional, Da Pieve, Chiara, additional, Barisa, Marta, additional, Ogunbiyi, Olumide, additional, Weitsman, Gregory, additional, Hutchinson, J. Ciaran, additional, Cross, Kate, additional, Biassoni, Lorenzo, additional, Stoyanov, Danail, additional, Sebire, Neil, additional, Beard, Paul, additional, De Coppi, Paolo, additional, Kramer-Marek, Gabriela, additional, Anderson, John, additional, and Giuliani, Stefano, additional

Published
2023
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17. Targeting of low ALK antigen density neuroblastoma using AND logic-gate engineered CAR-T cells

Author

Halliwell, Emma, primary, Vitali, Alice, additional, Muller, Henrike, additional, Alonso-Ferrero, Maria, additional, Barisa, Marta, additional, Gavriil, Artemis, additional, Piapi, Alice, additional, Leboreiro-Babe, Clara, additional, Gileadi, Talia, additional, Yeung, Jenny, additional, Pataillot-Meakin, Thomas, additional, Fisher, Jonathan, additional, Tucker, Lizzie, additional, Donovan, Laura, additional, Chesler, Lou, additional, Chester, Kerry, additional, and Anderson, John, additional

Published
2023
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19. Integrative analysis of neuroblastoma by single‐cell RNA sequencing identifies the NECTIN2‐TIGIT axis as a target for immunotherapy

Author

Wienke, Judith, primary, Visser, Lindy L, additional, Kholosy, Waleed M, additional, Keller, Kaylee M, additional, Barisa, Marta, additional, Munnings-Tomes, Sophie, additional, Carlton, Elizabeth, additional, Poon, Evon, additional, Rodriguez, Ana, additional, Bernardi, Ronald, additional, Van den Ham, Femke, additional, Van Hooff, Sander R, additional, Matser, Yvette A.H., additional, Tas, Michelle, additional, Langenberg, Karin P.S., additional, Lijnzaad, Philip, additional, Strijker, Josephine G.M., additional, Sanchez-Bernabeu, Alvaro, additional, Cornel, Annelisa M, additional, Holstege, Frank C.P., additional, Gray, Juliet C, additional, Tytgat, Lieve A.M., additional, De Krijger, Ronald, additional, Scheijde-Vermeulen, Marijn A, additional, Wijnen, Marc H.W.A., additional, Dierselhuis, Miranda P., additional, Straathof, Karin, additional, Behjati, Sam, additional, Wu, Wei, additional, Heck, Albert J.R., additional, Koster, Jan, additional, Nierkens, Stefan, additional, Chesler, Louis, additional, Anderson, John, additional, Caron, Hubert N, additional, Margaritis, Thanasis, additional, Van Noesel, Max M, additional, and Molenaar, Jan J, additional

Published
2022
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23. Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus

Author

Dougan, Stephanie K., Ashour, Joseph, Karssemeijer, Roos A., Popp, Maximilian W., Avalos, Ana M., Barisa, Marta, Altenburg, Arwen F., Ingram, Jessica R., Cragnolini, Juan Jose, Guo, Chunguang, Alt, Frederick W., Jaenisch, Rudolf, and Ploegh, Hidde L.

Subjects
Antigen-antibody reactions -- Research, B cells -- Physiological aspects, Influenza -- Development and progression -- Physiological aspects, Cell receptors -- Properties, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Influenza A virus-specific B lymphocytes and the antibodies they produce protect against infection (1). However, the outcome of interactions between an influenza haemagglutinin-specific B cell via its receptor (BCR) and virus is unclear. Through somatic cell nuclear transfer we generated mice that harbour B cells with a BCR specific for the haemagglutinin of influenza A/WSN/33 virus (FluBI mice). Their B cells secrete an immunoglobulin gamma 2b that neutralizes infectious virus. Whereas B cells from FluBI and control mice bind equivalent amounts of virus through interaction of haemagglutinin with surface-disposed sialic acids, the A/WSN/33 virus infects only the haemagglutinin-specific B cells. Mere binding of virus is not sufficient for infection of B cells: this requires interactions of the BCR with haemagglutinin, causing both disruption of antibody secretion and FluBI B-cell death within 18 h. In mice infected with A/WSN/33, lung-resident FluBI B cells are infected by the virus, thus delaying the onset of protective antibody release into the lungs, whereas FluBI cells in the draining lymph node are not infected and proliferate. We propose that influenza targets and kills influenza-specific B cells in the lung, thus allowing the virus to gain purchase before the initiation of an effective adaptive response., Memory B lymphocytes contribute to the protective immune response to flu infection by producing immunoglobulins that bind and neutralize the virus (1). The lung of an exposed individual contains influenza-specific [...]

Published
2013

26. Contributors

Author

Anderson, John, Barisa, Marta, Corsale, Anna Maria, Di Simone, Marta, Dieli, Francesco, Fisher, Jonathan, Fowler, Daniel, Meraviglia, Serena, Nair, Gaya, Nattress, Callum, Willcox, Benjamin E., and Willcox, Carrie R.

Published
2025
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28. Monoclonal iNKT cell mice reveal a role for both tissue of origin and the TCR in development of iNKT functional subsets

Author

Clancy-Thompson, Eleanor, Chen, Gui Zhen, Tyler, Paul M., Servos, Mariah M., Barisa, Marta, Brennan, Patrick J., Ploegh, Hidde L., and Dougan, Stephanie K.

Subjects
Cytotoxicity, Immunologic, B-Lymphocytes, Nuclear Transfer Techniques, Receptors, Antigen, T-Cell, alpha-beta, Interleukin-17, Kruppel-Like Transcription Factors, chemical and pharmacologic phenomena, Cell Differentiation, Nuclear Receptor Subfamily 1, Group F, Member 3, Article, Interleukin-10, Mice, Inbred C57BL, Mice, Organ Specificity, T-Lymphocyte Subsets, Animals, Cytokines, Natural Killer T-Cells, Promyelocytic Leukemia Zinc Finger Protein, T-Box Domain Proteins
Abstract

Invariant NKT (iNKT) cell functional subsets are defined by key transcription factors and output of cytokines, such as IL-4, IFN-γ, IL-17, and IL-10. To examine how TCR specificity determines iNKT function, we used somatic cell nuclear transfer to generate three lines of mice cloned from iNKT nuclei. Each line uses the invariant Vα14Jα18 TCRα paired with unique Vβ7 or Vβ8.2 subunits. We examined tissue homing, expression of PLZF, T-bet, and RORγt, and cytokine profiles and found that, although monoclonal iNKT cells differentiated into all functional subsets, the NKT17 lineage was reduced or expanded depending on the TCR expressed. We examined iNKT thymic development in limited-dilution bone marrow chimeras and show that higher TCR avidity correlates with higher PLZF and reduced T-bet expression. iNKT functional subsets showed distinct tissue distribution patterns. Although each individual monoclonal TCR showed an inherent subset distribution preference that was evident across all tissues examined, the iNKT cytokine profile differed more by tissue of origin than by TCR specificity.

Published
2017

30. Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus

Author

Massachusetts Institute of Technology. Department of Biology, Whitehead Institute for Biomedical Research, Jaenisch, Rudolf, Ploegh, Hidde, Dougan, Stephanie K., Ashour, Joseph, Karssemeijer, Roos A., Popp, Maximilian W., Avalos, Ana M., Barisa, Marta, Altenburg, Arwen F., Ingram, Jessica R., Cragnolini, Juan J., Guo, Chunguang, Alt, Frederick W., Massachusetts Institute of Technology. Department of Biology, Whitehead Institute for Biomedical Research, Jaenisch, Rudolf, Ploegh, Hidde, Dougan, Stephanie K., Ashour, Joseph, Karssemeijer, Roos A., Popp, Maximilian W., Avalos, Ana M., Barisa, Marta, Altenburg, Arwen F., Ingram, Jessica R., Cragnolini, Juan J., Guo, Chunguang, and Alt, Frederick W.

Abstract

Influenza A virus-specific B lymphocytes and the antibodies they produce protect against infection. However, the outcome of interactions between an influenza haemagglutinin-specific B cell via its receptor (BCR) and virus is unclear. Through somatic cell nuclear transfer we generated mice that harbour B cells with a BCR specific for the haemagglutinin of influenza A/WSN/33 virus (FluBI mice). Their B cells secrete an immunoglobulin gamma 2b that neutralizes infectious virus. Whereas B cells from FluBI and control mice bind equivalent amounts of virus through interaction of haemagglutinin with surface-disposed sialic acids, the A/WSN/33 virus infects only the haemagglutinin-specific B cells. Mere binding of virus is not sufficient for infection of B cells: this requires interactions of the BCR with haemagglutinin, causing both disruption of antibody secretion and FluBI B-cell death within 18 h. In mice infected with A/WSN/33, lung-resident FluBI B cells are infected by the virus, thus delaying the onset of protective antibody release into the lungs, whereas FluBI cells in the draining lymph node are not infected and proliferate. We propose that influenza targets and kills influenza-specific B cells in the lung, thus allowing the virus to gain purchase before the initiation of an effective adaptive response., National Institutes of Health (U.S.)

Published
2015

33. Shortwave Infrared Imaging Enables High-Contrast Fluorescence-Guided Surgery in Neuroblastoma.

Author

Privitera L, Waterhouse DJ, Preziosi A, Paraboschi I, Ogunlade O, Da Pieve C, Barisa M, Ogunbiyi O, Weitsman G, Hutchinson JC, Cross K, Biassoni L, Stoyanov D, Sebire N, Beard P, De Coppi P, Kramer-Marek G, Anderson J, and Giuliani S

Subjects
Child, Humans, Optical Imaging methods, Phantoms, Imaging, Coloring Agents, Fluorescent Dyes, Antineoplastic Agents, Neuroblastoma diagnostic imaging, Neuroblastoma surgery
Abstract

Fluorescence-guided surgery is set to play a pivotal role in the intraoperative management of pediatric tumors. Shortwave infrared imaging (SWIR) has advantages over conventional near-infrared I (NIR-I) imaging with reduced tissue scattering and autofluorescence. Here, two NIR-I dyes (IRDye800CW and IR12), with long tails emitting in the SWIR range, were conjugated with a clinical-grade anti-GD2 monoclonal antibody (dinutuximab-beta) to compare NIR-I and SWIR imaging for neuroblastoma surgery. A first-of-its-kind multispectral NIR-I/SWIR fluorescence imaging device was constructed to allow an objective comparison between the two imaging windows. Conjugates were first characterized in vitro. Tissue-mimicking phantoms, imaging specimens of known geometric and material composition, were used to assess the sensitivity and depth penetration of the NIR-I/SWIR device, showing a minimum detectable volume of ∼0.9 mm3 and depth penetration up to 3 mm. In vivo, fluorescence imaging using the NIR-I/SWIR device showed a high tumor-to-background ratio (TBR) for both dyes, with anti-GD2-IR800 being significantly brighter than anti-GD2-IR12. Crucially, the system enabled higher TBR at SWIR wavelengths than at NIR-I wavelengths, verifying SWIR imaging enables high-contrast delineation of tumor margins. This work demonstrates that by combining the high specificity of anti-GD2 antibodies with the availability and translatability of existing NIR-I dyes, along with the advantages of SWIR in terms of depth and tumor signal-to-background ratio, GD2-targeted NIR-I/SWIR-guided surgery could improve the treatment of patients with neuroblastoma, warranting investigation in future clinical trials., Significance: Multispectral near-infrared I/shortwave infrared fluorescence imaging is a versatile system enabling high tumor-to-background signal for safer and more complete resection of pediatric tumors during surgery., (©2023 The Authors; Published by the American Association for Cancer Research.)

Published
2023
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