Lini Pandite's research while affiliated with Adaptimmune US and other places

... Pazopanib is an efficient drug that significantly increases PFS in patients with locally advanced or metastatic RCC. 81,82 However, despite its efficacy and costeffectiveness, pazopanib has also been found to cause serious side effects in many patients, such as hepatotoxicity, hypertension, thrombocytopenia, anemia, fatigue, and diarrhea. Since toxicity is a common reason for treatment discontinuation, PK-guided dosing may prolong the time to discontinuation. ...

... After this, sunitinib, which has a broadspec trum activity against the FMS-like tyrosine kinase 3 (FLT3), a recep tor tyrosine kinase (KIT), fibroblast growth factor receptors (FGFR), Plateletderived growth factor receptors (PDGFR) and vascular en dothelial growth factor receptors (VEGFR), got approved by FDA for the treatment of renal cell carcinoma (RCC) and second line thera py of GIST (imatinibresistant gastrointestinal stromal tumour) [89]. Similarly, a drug sorafenib which effectively binds with the in active conformation of VEGFR kinase, was approved for the cure of RCC and hepatocellular carcinoma [90]. In 2009, a 2-amino pyrim idine derivative pazopanib was approved for the advanced stage of RCC. ...

... Ciclopirox, an antifungal cation chelator, and Lapatinib, a dual EGFR/HER2 inhibitor, showed analogous antitumoral activities coupled with the repression of E6/E7 transcription [102,103]. However, Lapatinib did not show overall benefit in a clinical trial, although enrolled patients were neither selected nor stratified based on EGFR/HER2 expression [104]. ...

... Recently, Hudes et al [34] demonstrated that patients affected by mRCC with specific tumor DNA copy number alterations (CNAs) are better responders to pazopanib. Particularly, the gain of chromosome 5q (5q+) seems to be related to a statistically significant longer PFS (P = 0.026). ...

... The first 60 patients demonstrated good disease control rates and thus led the Data and Safety Monitoring Committee to stop the discontinuation randomization phase and allow all patients to continue the drug. Out of the 225 patients enrolled with metastatic RCC, there was a 27% overall response rate by independent review at 12 weeks (Hutson et al. 2007). A double-blind phase III study of pazopanib 800 mg daily versus placebo in a 2:1 randomization of treatment-naive and cytokine-pretreated patients with metastatic RCC was recently reported (Sternberg et al. 2009). ...

... Pazopanib is a multi-tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, platelet-derived growth factor receptor (PDGFR)-a, PDGFR-b, fibroblast growth factor receptor (FGFR)-1, FGFR-3, and c-Kit. Pazopanib is approved as monotherapy for patients with advanced renal cell carci- noma [1] and soft tissue sarcoma [2] and is currently under investigation in multiple tumor types, including ovarian cancer, non-small-cell lung cancer, thyroid cancer, and cervical cancer34567. Gemcitabine is a cytotoxic nucleoside analogue of deoxycytidine whose triphosphate (dFdCTP) is irreversibly incorporated into DNA, subsequently inhibiting exonuclease and DNA repair activities. ...

... In addition, the levels of pHLA on the surface of some tumor cells can be low [17]. To overcome these problems, TCR affinity can be increased while maintaining specificity [18], thus improving tumor cell recognition and killing in vitro and in vivo [19][20][21][22], which leads to improved clinical efficacy across a range of tumor indications [23][24][25]. A key limitation of using HLA-dependent TCRs is that the HLA locus demonstrates polymorphism and therefore TCRs will typically be restricted to a specific HLA subtype [26]. ...