Application of short hydrophobic elastin-like polypeptides for expression and purification of active proteins

Yang, Chunguang; Lang, Ming-Fei; Fu, Xin; Lin, Heng; Zhang, Lichao; Ge, Gao-Shun; Sun, Jing; Hu, Xuejun

doi:10.1007/s13205-020-2139-0

Cited by 6 publications

(6 citation statements)

References 31 publications

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“…Complementing the findings from Ruella and coworkers, a more recent study demonstrated that CAR T cells with two discrete scFv domains, one against CD19 and the other against CD123, demonstrated cytotoxic effects against their corresponding targets both in vitro and in vivo. This further supports the idea that a dual CAR approach is effective in augmenting the response against leukemic blasts and reducing overall rates of disease relapse (106).…”

Section: Multi-targeting Cars 321 Dual-targeting Strategiessupporting

confidence: 77%

In Like a Lamb; Out Like a Lion: Marching CAR T Cells Toward Enhanced Efficacy in B-ALL

Kozani

O’Connor

2021

Molecular Cancer Therapeutics

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Combining synthetic biology with adoptive T-cell transfer has led to promising advances in the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), diffuse large B-cell lymphoma (DLBCL), and mantle cell lymphoma (MCL). Chimeric antigen receptors (CARs) are synthetic receptors that redirect T-cell specificity against cancer. CARs include “built-in” signaling domains that reprogram T-cell metabolism, enhance effector function, and support long-term persistence. Despite their success in blood-based malignancies, relapse can occur in CD19-redirected CAR T-cell therapies for several reasons, including poor engraftment, impaired in vivo proliferation, and T-cell senescence. Herein, we explain how subtle alterations in CAR design may overcome barriers to effective adoptive immunotherapy. We also discuss how the physiochemical properties of the single-chain variable fragment (scFv) affect differentiation and persistence. Moreover, we describe innovative advances in CAR engineering and provide insight into the development of humanized scFvs whose proposed benefits include increased persistence and improved clinical outcomes. Tumor cells can evade CAR T-cell–mediated detection and elimination due to the emergence or presence of CD19-negative leukemic cell subpopulations. We also discuss the opportunities and challenges in targeting other B-ALL–associated antigens. Identifying alternate targets is fundamentally necessary to restore the success of CAR T-cell therapies in CD19-negative patients with B-ALL.

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Section: Multi-targeting Cars 321 Dual-targeting Strategiessupporting

confidence: 77%

In Like a Lamb; Out Like a Lion: Marching CAR T Cells Toward Enhanced Efficacy in B-ALL

Kozani

O’Connor

2021

Molecular Cancer Therapeutics

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“…The transition temperature was calculated as described previously. [49,50] Gelation. A 150 µL solution of E5C in 1xPBS, pH 7.4 placed in a 2 mL glass vial was incubated at 37 °C at a concentration of 1 mM.…”

Section: Dynamic Light Scatteringmentioning

confidence: 99%

Injectable Progranulin-derivative Atsttrin loaded Protein Engineered Gels for Post Traumatic Osteoarthritis

Katyal

Hettinghouse

Meleties

et al. 2021

Preprint

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Protein-based biomaterials offer several advantages over synthetic materials, owing to their unique stimuli-responsive properties, biocompatibility and modular nature. We have successfully developed protein block polymers that consist of elastin like polypeptide (E) and the coiled-coil domain of cartilage oligomeric matrix protein (C). Here, we demonstrate that E5C, a construct consisting of five repeats of E and a single domain of C, is capable of forming a porous networked gel at physiological temperature, making it an excellent candidate for injectable biomaterials. Combination of E5C with Atsttrin, a chondroprotective engineered derivative of anti-inflammatory growth factor progranulin (PGRN), provides a unique biochemical and biomechanical environment to protect against post-traumatic osteoarthritis (PTOA) onset and progression. E5C gel was demonstrated to provide prolonged release of Atsttrin and inhibit chondrocyte catabolism while facilitating anabolic signaling in vitro. We also provide in vivo evidence that prophylactic and therapeutic application of Atsttrin-loaded E5C hydrogels protected against PTOA onset and progression in a rabbit anterior cruciate ligament transection model. Collectively, we have developed a unique protein-based gel capable of minimally invasive, sustained delivery of prospective therapeutics, particularly the PGRN-derivative Atsttrin, for prevention of OA onset and progression.

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“…If the guest residue Xaa is Pro, the conformation of the ELP chain is disrupted, which destroys the principal characteristic and useful feature of the biopolymer, i.e., its inverse thermal transition property [ 13 ]. Custom design of an ELP core sequence with specific amino acids and sequence length with subsequent specialized modifications and functionalization can help to precisely control its environmental reactivity, mechanical properties and cellular metabolic pathways [ 14 , 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Application of Elastin-like Polypeptide in Tumor Therapy

Shi

Chen

Liu

et al. 2022

Cancers

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Elastin-like polypeptides (ELPs) are stimulus-responsive artificially designed proteins synthesized from the core amino acid sequence of human tropoelastin. ELPs have good biocompatibility and biodegradability and do not systemically induce adverse immune responses, making them a suitable module for drug delivery. Design strategies can equip ELPs with the ability to respond to changes in temperature and pH or the capacity to self-assemble into nanoparticles. These unique tunable biophysicochemical properties make ELPs among the most widely studied biopolymers employed in protein purification, drug delivery, tissue engineering and even in tumor therapy. As a module for drug delivery and as a carrier to target tumor cells, the combination of ELPs with therapeutic drugs, antibodies and photo-oxidation molecules has been shown to result in improved pharmacokinetic properties (prolonged half-life, drug targeting, cell penetration and controlled release) while restricting the cytotoxicity of the drug to a confined infected site. In this review, we summarize the latest developments in the application methods of ELP employed in tumor therapy, with a focus on its conjugation with peptide drugs, antibodies and photosensitizers.

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Application of short hydrophobic elastin-like polypeptides for expression and purification of active proteins

Cited by 6 publications

References 31 publications

In Like a Lamb; Out Like a Lion: Marching CAR T Cells Toward Enhanced Efficacy in B-ALL

In Like a Lamb; Out Like a Lion: Marching CAR T Cells Toward Enhanced Efficacy in B-ALL

Injectable Progranulin-derivative Atsttrin loaded Protein Engineered Gels for Post Traumatic Osteoarthritis

Application of Elastin-like Polypeptide in Tumor Therapy

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