Chimeric antigen receptor (CAR) T-cell therapy has shown promise in the treatment of haematological cancers and is currently being investigated for solid tumours, including high-grade glioma brain tumours. There is a desperate need to quantitatively study the factors that contribute to the efficacy of CAR T-cell therapy in solid tumours. In this work, we use a mathematical model of predator–prey dynamics to explore the kinetics of CAR T-cell killing in glioma: the Chimeric Antigen Receptor T-cell treatment Response in GliOma (CARRGO) model. The model includes rates of cancer cell proliferation, CAR T-cell killing, proliferation, exhaustion, and persistence. We use patient-derived and engineered cancer cell lines with an in vitro real-time cell analyser to parametrize the CARRGO model. We observe that CAR T-cell dose correlates inversely with the killing rate and correlates directly with the net rate of proliferation and exhaustion. This suggests that at a lower dose of CAR T-cells, individual T-cells kill more cancer cells but become more exhausted when compared with higher doses. Furthermore, the exhaustion rate was observed to increase significantly with tumour growth rate and was dependent on level of antigen expression. The CARRGO model highlights nonlinear dynamics involved in CAR T-cell therapy and provides novel insights into the kinetics of CAR T-cell killing. The model suggests that CAR T-cell treatment may be tailored to individual tumour characteristics including tumour growth rate and antigen level to maximize therapeutic benefit.

Objectives: Calcified cysticercus larva with perilesional abnormality is thought to be responsible for seizures in patients with neurocysticercosis (NCC). However, it is not well understood why some calcified cysts are associated with seizures even without perilesional abnormality. Methods: The study group consists of 30 subjects from an ongoing survey for disease burden estimation of a swine farming community who had a single calcified lesion without any perilesional abnormality with or without presentation of seizures. Each group consisted of 15 patients with calcified cysts and was labeled as asymptomatic and symptomatic. We performed dynamic contrast-enhanced (DCE) MRI on all these subjects and determined serum matrix metalloproteinase-9 (MMP-9) levels and MMP-9 gene polymorphisms. Results: DCE-MRI–derived rate transfer constant (k_ep) and serum MMP-9 levels showed significant differences between symptomatic and asymptomatic subjects. We observed an increase in the MMP-9 levels, k_ep, and the volume transfer coefficient (k^trans) in these lesions. We also observed a significant increase in MMP-9 (R279Q) gene polymorphism in symptomatic subjects compared with asymptomatic and control subjects. Conclusions: Perilesional inflammation, which varies from symptomatic to asymptomatic subjects, can be quantified using DCE-MRI in calcified cysticercosis and may help distinguish these 2 groups with similar imaging findings. The observed increase in k_ep with serum MMP-9 levels suggests that the former may serve as a biomarker of MMP-9 levels in these subjects. The significant MMP-9 (R279Q) gene polymorphism in symptomatic subjects might explain the differences in the observed DCE-MRI indices between symptomatic and asymptomatic subjects.

The study was performed to compare dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) with 3-dimensional (3D) pseudocontinuous arterial spin labeling (PCASL) MRI in gliomas with an aim to see whether arterial spin labeling (ASL)-derived cerebral blood flow (CBF) values can be used as an alternative to DCE-MRI for its grading. Sixty-four patients with glioma (37 male; mean age, 43 years; 38 high grade and 26 low grade) underwent 3D-PCASL and DCE-MRI. The DCE indices (relative cerebral blood volume, rCBV; relative CBF, rCBF; permeability, k and kep; and leakage, ve) and ASL (absolute and rCBF) values were quantified from the tumors. Student independent t test was used to compare ASL and DCE-MRI indices. Pearson correlation was used to see correlation between DCE- and ASL-derived CBF values in tumor and normal parenchyma. On Student t test, neither ASL-derived absolute CBF (P = 0.78) nor rCBF (P = 0.12) values were found to be significantly different in 2 groups, whereas DCE indices except ve were significantly higher in high-grade gliomas. Arterial spin labeling-derived rCBF values weakly correlated with DCE-derived rCBF values, whereas these did not show correlation in normal grey (P = 0.12, r = 0.2) and white (P = 0.26, r = 0.14) matter regions. Three-dimensional pseudocontinuous arterial spin labeling does not appear to be a reliable technique in the current form and may not be a suitable replacement for DCE in grading of glioma.

BACKGROUND AND PURPOSE: Epileptogenesis in NCC is associated with perilesional inflammation and disruption in BBB. We quantified BBB in different stages of NCC by using DCE-MR imaging to look for the differences in perfusion indices and to correlate these indices with serum MMP-9 expression. MATERIALS AND METHODS: DCE-MR imaging along with conventional MR imaging was performed in 57 single cysticercous brain lesions to quantify the k_ep, K^trans, and v_e around the lesions, which were in different stages of evolution. There were 6 lesions in the vesicular stage and 17 lesions each in the colloidal, granular-nodular, and calcified stages. Serum MMP-9 was quantified from all patients, whereas perfusion indices were quantified from all stages except for the vesicular stage. RESULTS: We observed significant differences among the 3 stages of NCC in serum MMP-9 expression as well as DCE-derived k_ep values. In addition, k_ep showed a strongly significant positive correlation with MMP-9 expression when modeled with the individual stage of the disease as well as with all stages when pooled together. Other DCE-derived hemodynamic and pharmacokinetic parameters showed inconsistent differences with each stage of the disease. The correlation of DCE-derived parameters with serum MMP-9 expression and edema volume also showed inconsistency with the stage of the disease. CONCLUSIONS: We conclude that k_ep correlates best with serum MMP-9 expression among the pharmacokinetic indices and most closely represents the degree of BBB breakdown, which is highest in the colloidal stage and lowest in the calcified stage. k_ep may be used as a noninvasive image biomarker of BBB breakdown in different stages of NCC.