RESUMO
Cancer treatment is one of the fundamental challenges in clinical setting, especially in relapsed/refractory malignancies. The novel immunotherapy-based treatments bring new hope in cancer therapy and achieve various treatment successes. One of the distinguished ways of cancer immunotherapy is adoptive cell therapy, which utilizes genetically modified immune cells against cancer cells. Between different methods in ACT, the chimeric antigen receptor T cells have more investigation and introduced a promising way to treat cancer patients. This technology progressed until it introduced six US Food and Drug Administration-approved CAR T cell-based drugs. These drugs act against hematological malignancies appropriately and achieve exciting results, so they have been utilized widely in cell therapy clinics. In this review, we introduce all CAR T cells-approved drugs based on their last data and investigate them from all aspects of pharmacology, side effects, and compressional. Also, the efficacy of drugs, pre- and post-treatment steps, and expected side effects are introduced, and the challenges and new solutions in CAR T cell therapy are in the last speech.
Assuntos
Imunoterapia Adotiva , Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva/métodos , Animais , Receptores de Antígenos Quiméricos/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Receptores de Antígenos de Linfócitos T/imunologiaRESUMO
BACKGROUND: Low-grade inflammation and stress oxidative condition play a role in the pathogenesis of obesity, and the serum levels of these markers, such as pro-oxidant-antioxidant balance (PAB), high-sensitivity C-reactive protein (hs-CRP), and uric acid may indicate obesity progression. In this study, we aimed to investigate the relationship between obesity with PAB, hs-CRP, and uric acid in the Iranian population. METHODS: This study was derived from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. A total of 7985 subjects aged 35 to 65 years were divided into three groups according to body mass index (BMI) as: normal, overweight and obese groups. Anthropometric indices and biochemical parameters such as PAB, superoxide dismutase type 1 (SOD1), hs-CRP, and uric acid were measured in all the participants. We evaluated the association of obesity with inflammatory factors by using multivariate regression analysis. Also, those participants with hypertension, an endocrine disorder, history of cardiovascular diseases and diabetes mellitus were excluded from the study. RESULTS: There was a positive significant correlation between BMI and serum PAB, hs-CRP and uric acid (p < 0.001). While no statistically significant relation was observed between BMI and SOD1 (p = 0.85). Multivariate regression analysis showed that the risk of overweight and obesity increased 1.02 and 1.03-fold according to increase 10 units of PAB raise in comparison to reference group (normal weight) [(odds ratio (OR): 1.02, 95% CI (1.01-1.03)] and [OR: 1.03, 95% CI (1.01-1.04)], respectively). In addition, hs-CRP serum concentration was significantly associated with a high risk of obesity [(OR: 1.02; 95% CI (1.01-1.03)]. While the high levels of serum uric acid were associated with increased odds of overweight and obesity risk [OR: 1.4; CI (1.39-1.58) and OR: 1.76; CI (1.63-1.89), respectively]. CONCLUSIONS: Generally, we showed a significant association between BMI and serum PAB, hs-CRP values and uric acid levels, suggesting the role of these factors as risk stratification factors for obesity.
Assuntos
Biomarcadores , Índice de Massa Corporal , Proteína C-Reativa , Inflamação , Obesidade , Estresse Oxidativo , Ácido Úrico , Humanos , Masculino , Obesidade/sangue , Obesidade/epidemiologia , Obesidade/complicações , Irã (Geográfico)/epidemiologia , Pessoa de Meia-Idade , Feminino , Biomarcadores/sangue , Adulto , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Inflamação/sangue , Inflamação/epidemiologia , Idoso , Ácido Úrico/sangue , Estudos de Coortes , Seguimentos , Prognóstico , Fatores de RiscoRESUMO
Equipping cancer-fighting immune cells with chimeric antigen receptor (CAR) has gained immense attention for cancer treatment. CAR-engineered T cells (CAR T cells) are the first immune-engineered cells that have achieved brilliant results in anti-cancer therapy. Despite promising anti-cancer features, CAR T cells could also cause fatal side effects and have shown inadequate efficacy in some studies. This has led to the introduction of other candidates for CAR transduction, e.g., Natural killer cells (NK cells). Regarding the better safety profile and anti-cancer properties, CAR-armored NK cells (CAR NK cells) could be a beneficial and suitable alternative to CAR T cells. Since introducing these two cells as anti-cancer structures, several studies have investigated their efficacy and safety, and most of them have focused on hematological malignancies. Solid tumors have unique properties that make them more resistant and less curable cancers than hematological malignancies. In this review article, we conduct a comprehensive review of the structure and properties of CAR NK and CAR T cells, compare the recent experience of immunotherapy with CAR T and CAR NK cells in various solid cancers, and overview current challenges and future solutions to battle solid cancers using CARNK cells.