Background: Improving T cell trafficking to tumors may help augment anti-tumor responses in ACT using tumor infiltrating lymphocytes (TILs). mm produces the chemokines CXCL1 and CXCL8, which are thought to promote autocrine growth and angiogenesis. However, tumor antigen-specific T cells frequently fail to express the chemokine receptors specific for these ligands, including CXCR2. We have generated modified T cells using retroviral vectors encoding CXCR2 [Kershaw et al. Hum Gene Ther. 2002; 3: 1971-80]. These transduced cells exhibit enhanced trafficking to CXCL1 expressing tumors, leading to improved anti-tumor responses and survival in preclinical models [Peng et al. Cancer Res. 2010; 16: 5458-68]. Methods: Pts with mm who have previously had T cells harvested and cryopreserved at MDACC with disease amenable to serial biopsy with excellent PS and organ function are eligible to enroll. All pts receive a standard conditioning regimen consisting of 7 days of cyclophosphamide and fludarabine for lymphodepletion, followed by infusion of pooled ex-vivo expanded TIL transduced with CXCR2, Nerve Growth Factor Receptor (NGFR) and non-virally transduced TIL followed by high dose IL-2 (720,000 IU/kg IV q 8 hrs up to 15 doses) (NCT 01740557). The NGFR is truncated to render it incapable of eliciting intracellular signaling and will serve as a control for T cell trafficking since human T cells do not express NGFR. Patients have mandatory biopsy prior to lymphodepletion and then at day 21 to allow for assessment of chemokine levels and quantification of CXCR2 and NGFR transduced T cells. There are 5 dose levels of infused CXCR2 transduced cells to be studied including 15, 30, 45, 60, 75 x 10⁹ T cells. Currently 3 patients out of a planned 36 have been enrolled and treated. The primary objective is to determine the safety and toxicity of CXCR2 transduced TIL. Secondary objectives include assessing if CXCR2 transduction enhances TIL ability to migrate to tumors. Levels of CXCL1 and CXCL8 in tumor tissue will be assessed and correlated with tumor localization of CXCR2 transduced TIL and clinical outcomes. Clinical trial information: NCT 01740557.