Syngeneic murine glioblastoma models: reactionary immune changes and immunotherapy intervention outcomes

Abstract

Glioblastoma is the most common primary malignant brain neoplasm with dismal 10-year survival rates of < 1%. Despite promising preliminary results from several novel therapeutic agents, clinical responses have been modest due to several factors, including tumor heterogeneity, immunosuppressive tumor microenvironment, and treatment resistance. Novel immunotherapeutics have been developed to reverse tumor-induced immunosuppression in patients with glioblastomas. In order to recapitulate the tumor microenvironment, reliable in vivo syngeneic murine models are critical for the development of new targeted agents as these models demonstrate rapid tumor induction and reliable tumor growth over multiple generations. Despite the clear advantages of murine models, choosing an appropriate model from an immunological perspective can be difficult and have significant ramifications on the translatability of the results from murine to human trials. Herein, the authors reviewed the 4 most commonly used immunocompetent syngeneic murine glioma models (GL261 [C57BL/6], SB28 [C57BL/6], CT-2A [C57BL/6], and SMA-560 [VM/Dk]) and compared their strengths and weaknesses from an immunological standpoint.

Is local autogenous morselized bone harvested from decompression through a posterior-transforaminal approach sufficient for single-level interbody fusion in the lower lumbar spine?

“…In the present study, the final fusion rate of grade 4 or 5 was achieved in 96.6% of patients, which was comparable with previous studies [12,13,21,22]. Our results also concur with the findings of studies using other bone grafts and biologics to achieve comparable fusion rates: 89.6% using bioactive glasslocal autograft mixtures, 91.6% using autograft, 95.8% or 98.3% using iliac crest, and 94.1% using rhBMP-2 and local bone graft at 1-year follow-up [9,12,13,22]. These results establish not only the applicability of LAMB for interbody fusion in the lower lumbar spine but also the fact that the volume of LAMB harvested from the decompression is sufficient to achieve fusion at a single level.…”

“…An autologous iliac crest bone graft (ICBG) is considered the gold standard in terms of the aforementioned properties [4]; however, its use is limited due to the associated donor site pain, a limited supply of bone graft, and the need for additional surgical invasion [5,6]. Therefore, alternative grafting materials, such as allografts, ceramics, demineralized bone matrix, and recombinant human bone morphogenetic proteins 2 and 7 (rhBMP-2 and 7) have been used in the clinical practice [7][8][9]. Although some of these materials are highly effective, their widespread use is hampered by certain limitations, such as the absence of osteogenic properties, the transmission risk for blood-borne pathogens, adverse or fatal events, and tremendous medical costs [7][8][9][10].…”

“…Therefore, alternative grafting materials, such as allografts, ceramics, demineralized bone matrix, and recombinant human bone morphogenetic proteins 2 and 7 (rhBMP-2 and 7) have been used in the clinical practice [7][8][9]. Although some of these materials are highly effective, their widespread use is hampered by certain limitations, such as the absence of osteogenic properties, the transmission risk for blood-borne pathogens, adverse or fatal events, and tremendous medical costs [7][8][9][10].…”

IL7 and IL7 Flt3L co-expressing CAR T cells improve therapeutic efficacy in mouse EGFRvIII heterogeneous glioblastoma

“…Transplantable tumor cell lines tend to be more immunogenic and elicit nonnaturally occurring immune responses compared to genetically induced mouse models. We chose the CT2A mouse model due to its low immunogenicity and immunosuppressive microenvironment compared to GL261 and SMA-560 models (87,88). However, CT2A tumors can be less correlated to patient immune phenotypes than GL261 tumors and can become immunologically active after surgical resection (89).…”

Research Status of Mouse Models for Non-Small-Cell Lung Cancer (NSCLC) and Antitumor Therapy of Traditional Chinese Medicine (TCM) in Mouse Models

“…This allows for evaluation of toxicities, including on-target/off-tumor side effects, and the immunosuppressive microenvironments [ 53 ]. Now, due to the growing worldwide enthusiasm in cancer immunotherapy, syngeneic murine models are widely used tools for studying tumor immunity and immunotherapy response because there is a fully functional murine immune system [ 51 , 54 , 55 ].…”