Adoptive Immunotherapy for Cancer or Viruses

Maus, Marcela V.; Fraietta, Joseph A.; Levine, Bruce L.; Kalos, Michael; Zhao, Yangbing; June, Carl H.

doi:10.1146/annurev-immunol-032713-120136

Cited by 250 publications

(238 citation statements)

References 204 publications

Supporting

Mentioning

226

Contrasting

Unclassified

Order By: Relevance

“…Thus, cancer cells can fool T-cells in two ways corresponding respectively to (a) or/ and (b) above, namely, stop producing MHC on their surfaces or display a form of co-stimulatory ligands that act as off-switches. To overcome these two eventualities, the CAR technology (see [8][9][10][11][12] has made it possible to genetically modify ("engineer") the T-cells in either of two ways so that, (a) instead of the D-(dendritic cells), the T-cells could home-in directly on antigens that may be abundant on cancer cells without necessarily being presented by the MHC molecules, or else (b) obviating altogether the need for the two-step process described earlier for attacking the cancer cells.…”

Section: Systemic Immunotherapymentioning

confidence: 99%

See 1 more Smart Citation

Immunotherapy of Brain Cancers and Neurological Disorders

Fymat¹

2017

JCPCR

View full text Add to dashboard Cite

Section: Systemic Immunotherapymentioning

confidence: 99%

“…It has been tested in dozens of studies (~ 1,000 patients) in certain types of cancers (leukemia and lymphoma). Half or more of these patients are now living longer than expected and hundreds appear to be cancer-free [10].…”

Section: On the Chimeric Antigen Receptor T-therapymentioning

confidence: 99%

Immunotherapy of Brain Cancers and Neurological Disorders

Fymat¹

2017

JCPCR

View full text Add to dashboard Cite

“…In vitro T-cell expansion is achieved with signals mimicking normal T-cell activation [1]. Signaling through CD3 and CD28 in vivo provokes autonomous IL-2 production by the activated T cells, which is central to clonal expansion.…”

Section: Introductionmentioning

confidence: 99%

Low interleukin-2 concentration favors generation of early memory T cells over effector phenotypes during chimeric antigen receptor T-cell expansion

et al. 2017

View full text Add to dashboard Cite

Background. Adoptive T-cell therapy offers new options for cancer treatment. Clinical results suggest that T-cell persistence, depending on T-cell memory, improves efficacy. The use of interleukin (IL)-2 for in vitro T-cell expansion is not straightforward because it drives effector T-cell differentiation but does not promote the formation of T-cell memory. We have developed a cost-effective expansion protocol for chimeric antigen receptor (CAR) T cells with an early memory phenotype. Methods. Lymphocytes were transduced with third-generation lentiviral vectors and expanded using CD3/CD28 microbeads. The effects of altering the IL-2 supplementation (0-300 IU/mL) and length of expansion (10-20 days) on the phenotype of the T-cell products were analyzed. Results. High IL-2 levels led to a decrease in overall generation of early memory T cells by both decreasing central memory T cells and augmenting effectors. T memory stem cells (TSCM, CD95 + CD45RO − CD45RA + CD27 + ) were present variably during T-cell expansion. However, their presence was not IL-2 dependent but was linked to expansion kinetics. CD19-CAR T cells generated in these conditions displayed in vitro antileukemic activity. In summary, production of CAR T cells without any cytokine supplementation yielded the highest proportion of early memory T cells, provided a 10-fold cell expansion and the cells were functionally potent. Discussion. The number of early memory T cells in a T-cell preparation can be increased by simply reducing the amount of IL-2 and limiting the length of T-cell expansion, providing cells with potentially higher in vivo performance. These findings are significant for robust and cost-effective T-cell manufacturing.

show abstract

“…This nascent field is often referred to as immunoengineering, and we will focus this review on the major challenges and opportunities that exist in facilitating and enabling the translation of promising new immunotherapeutic strategies into the clinic. This perspective will not attempt to exhaustively review the field of cancer immunotherapy (1,(5)(6)(7)(8)(9)(10) or the field of nanomaterial vaccines (11)(12)(13)(14)(15)(16), topics that are well covered in recent reviews. Instead we will focus on the technical challenges that exist in translating the principles of cancer immunotherapy into clinical reality: what approaches are being used, and where opportunities exist for new ideas and development.…”

mentioning

confidence: 99%

Engineering opportunities in cancer immunotherapy

Jeanbart

Swartz

2015

Proc. Natl. Acad. Sci. U.S.A.

113

View full text Add to dashboard Cite

Immunotherapy has great potential to treat cancer and prevent future relapse by activating the immune system to recognize and kill cancer cells. A variety of strategies are continuing to evolve in the laboratory and in the clinic, including therapeutic noncellular (vector-based or subunit) cancer vaccines, dendritic cell vaccines, engineered T cells, and immune checkpoint blockade. Despite their promise, much more research is needed to understand how and why certain cancers fail to respond to immunotherapy and to predict which therapeutic strategies, or combinations thereof, are most appropriate for each patient. Underlying these challenges are technological needs, including methods to rapidly and thoroughly characterize the immune microenvironment of tumors, predictive tools to screen potential therapies in patient-specific ways, and sensitive, information-rich assays that allow patient monitoring of immune responses, tumor regression, and tumor dissemination during and after therapy. The newly emerging field of immunoengineering is addressing some of these challenges, and there is ample opportunity for engineers to contribute their approaches and tools to further facilitate the clinical translation of immunotherapy. Here we highlight recent technological advances in the diagnosis, therapy, and monitoring of cancer in the context of immunotherapy, as well as ongoing challenges.immunoengineering | cancer vaccine | adoptive T-cell therapy | diagnostic tools | checkpoint blockade

show abstract

Adoptive Immunotherapy for Cancer or Viruses

Cited by 250 publications

References 204 publications

Immunotherapy of Brain Cancers and Neurological Disorders

Immunotherapy of Brain Cancers and Neurological Disorders

Low interleukin-2 concentration favors generation of early memory T cells over effector phenotypes during chimeric antigen receptor T-cell expansion

Engineering opportunities in cancer immunotherapy

Contact Info

Product

Resources

About