Massive clonal expansion of medulloblastoma-specific T cells during adoptive cellular therapy

Flores, Catherine; Wildes, Tyler J.; Dean, Bayli DiVita; Moore, Ginger; Drake, Jeffrey; Abraham, Rebecca; Gil, Jorge; Yegorov, Oleg; Yang, Changlin; Dean, Joseph; Moneypenny, Craig G.; Shin, David; Pham, Christina; Krauser, Jeanne; King, James; Grant, Gerald A.; Driscoll, Timothy A.; Kurtzberg, Joanne; McLendon, Roger E.; Gururangan, Sridharan; Mitchell, Duane A.

doi:10.1126/sciadv.aav9879

Cited by 22 publications

(21 citation statements)

References 17 publications

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“…It has been previously reported that spectratyping using fluorescence-activated cell sorting (FACS) analysis of TCR V may be used to track the reactivity of specific TCR V families towards target cells [43][44][45]. For validation of this method, we verified the reactivity of TCR V 5.1, 5.2 T-cells for OVA-expressing target cells [46] (Supp.…”

Section: Individual Tumor Escape Variants Are Immunologically Distincmentioning

confidence: 95%

“…Tumor-reactive T-cells were generated as previously described [29][30][31]40]. For TOGA tumors were utilized identically to KR158B-luc tumors.…”

Section: Adoptive Cellular Therapymentioning

confidence: 99%

“…S1D). In a recent manuscript, we discovered that the primary TCR V family that drives ACT response to KR158B-luc in vivo is TCR V6 [45]. We therefore FACS-sorted TCR V6 + T-cells from the polyclonal KR158B-luc T-cell pool.…”

Section: Individual Tumor Escape Variants Are Immunologically Distincmentioning

confidence: 99%

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Immune Escape After Adoptive T-cell Therapy for Malignant Gliomas

Wildes

Dyson

Francis

et al. 2020

Clinical Cancer Research

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Section: Individual Tumor Escape Variants Are Immunologically Distincmentioning

confidence: 95%

“…Tumor-reactive T-cells were generated as previously described [29][30][31]40]. For TOGA tumors were utilized identically to KR158B-luc tumors.…”

Section: Adoptive Cellular Therapymentioning

confidence: 99%

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Immune Escape After Adoptive T-cell Therapy for Malignant Gliomas

Wildes

Dyson

Francis

et al. 2020

Clinical Cancer Research

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“…We can also use DCs pulsed with a tumor RNA transcriptome to expand polyclonal tumor-reactive T cells during adoptive T cell therapies in medulloblastoma. 55 In general, DCs are the feasible option regarding the specific loading of treatment agents to achieve effective antitumor immunization, and further exploration of DCs in the immunotherapeutic treatment of medulloblastomas is warranted.…”

Section: Dendritic Cells (Dcs)mentioning

confidence: 99%

“…We can also use DCs pulsed with a tumor RNA transcriptome to expand polyclonal tumor‐reactive T cells during adoptive T cell therapies in medulloblastoma. 55 …”

Section: Immune Cell Landscape Of Medulloblastomamentioning

confidence: 99%

Immune cell landscape and immunotherapy of medulloblastoma

Jin

Wang

2021

Pediatric Investigation

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Medulloblastoma is the most common primary pediatric malignancy of the central nervous system. Recurrent and refractory patients account for approximately 30% of them. Immune cells are an important component of the brain tumor microenvironment, including tumor-associated macrophages, T lymphocytes, natural killer cells, dendritic cells, neutrophils and B lymphocytes. Understanding how they behave and interact is important in the investigation of the onset and progression of medulloblastoma. Here, we overview the features and recent advances of each component of immune cells in medulloblastoma. Meanwhile, immunotherapy is a promising but also challenging treatment strategy for medulloblastoma. At present, there are a growing number of immunotherapeutic approaches under investigation including immune checkpoint inhibitors, oncolytic viruses, cancer vaccines, chimeric antigen receptor T cell therapies, and natural killer cells in recurrent and refractory medulloblastoma patients.

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Recent Advances in Delivery Systems for Genetic and Other Novel Vaccines

et al. 2022

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including yellow fever, polio, diphtheria, rubella, smallpox, mumps, and measles in humans; and equine infectious anemia, classic swine fever, and cattle plague in animals. The successful prevention of these diseases has saved millions of lives, as well as time and efforts in health care. However, conventional vaccines are usually not effective as therapeutic measures, and often fail to provide sufficient protections against some diseases. Therefore, many major diseases, such as the malaria, tuberculosis, dengue, human immunodeficiency virus (HIV) infections, and cancer, still lack effective vaccines, and developing vaccines for them remains challenging. [5][6][7] Though many autoimmune diseases are also difficult to vaccinate, we excluded this type of diseases in the review due to their highly variable and unique mechanisms.There are various factors that may influence the outcomes of vaccines. An important discovery of modern immunology is that robust cellular immune responses with strong CD8 + T cell activities may significantly improve vaccination outcome against some of these hard-to-vaccinate diseases. This is particularly the case when the pathogens can lurk in infected cells for a long period of time (e.g., HIV) or the cells themselves became malfunctional (e.g., cancer). However, conventional vaccines often suffer from imprecise control of vaccine activity in vivo (e.g., targeted accumulation and selective cell uptake) which leads to insufficient/inappropriate immune responses or short immune memory; hence, they may become less effective in these situations. [7][8][9] Besides, rapid vaccine development, targeted epitope optimization, and other novel strategies are regarded to be important for successful prevention of infections from viral pathogens with high mutation rates (e.g., the highly variable influenza virus) which often quickly become resistant to existing vaccines. [10,11] With the advances in biological and pharmaceutical technologies, a series of new vaccines have been developed, including the famous subunit vaccines (including bioengineered protein, protein fragments, and peptides) and genetic vaccines (normally DNA-and RNA-based vaccines). These alternative vaccines provide new possibilities for preventing hard-to-vaccinate diseases by using carefully selected components of the pathogens or diseased cells as vaccine immunogens based on in-depth understanding of the immune response activation processes. More specifically, characteristic proteins/peptides Vaccination is one of the most successful and cost-effective prophylactic measures against diseases, especially infectious diseases including smallpox and polio. However, the development of effective prophylactic or therapeutic vaccines for other diseases such as cancer remains challenging. This is often due to the imprecise control of vaccine activity in vivo which leads to insufficient/inappropriate immune responses or short immune memory. The development of new vaccine types in recent decades has created the potential for improving the prot...

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Massive clonal expansion of medulloblastoma-specific T cells during adoptive cellular therapy

Abstract: Extensive clonal T cell expansion is associated with response to immunotherapy.

Cited by 22 publications

References 17 publications

Immune Escape After Adoptive T-cell Therapy for Malignant Gliomas

Immune Escape After Adoptive T-cell Therapy for Malignant Gliomas

Immune cell landscape and immunotherapy of medulloblastoma

Recent Advances in Delivery Systems for Genetic and Other Novel Vaccines

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