Tumor Infiltrating Lymphocytes (TILs) Therapy – Report of the First TILs Therapy Infusion from India, for a Patient of Malignant Melanoma

Relapsed metastatic malignant melanoma (RMMM) is incurable. Newer research- based therapies like Tumor Infiltrating Lymphocyte therapy (TILs) hold promise for these patients. We present the report of a TILs therapy infusion that we performed for a patient with RMMM which, to our knowledge, is the first such infusion from India. Our patient was a 42-year Female, diagnosed in July 2022 with a localized melanoma on left foot. She underwent repeated wide local excisions but in a short while progressed as RMMM. She was BRAF wild type. She was diagnosed earlier with Papillon Lefevre's syndrome and had a family history of the same. She received 3 cycles of Pembrolizumab and 2 cycles of Ipilimumab/Nivolumab but progressed rapidly and palliative radiotherapy to multiple sites. The patient expressed her desire to undergo TILs therapy and enquiries were made with various international centres for clinical trials but was not successful. Permission was obtained from the Drugs Control General of India and Institutional ethics committee to perform the same in India after engineering it at Elvenia Regenerative, Malaysia. An inguinal lymph node excision sample was sent for processing. In the interim she was administered weekly paclitaxel-carboplatin as a bridge till the same, to which she had a stable disease. Prior to cell therapy her PET CT showed metastasis to multiple sites including bone, liver, lung, lymph nodes, soft tissue, and an asymptomatic brain lesion. TILs were isolated from the tumor tissue, underwent rapid expansion and co-culturing with neoantigen/irradiated feeder cells (TMGs/synthetic peptide sequence, which was autologous from the patient, 2 × 108), IL-2, and anti-CD3 antibodies (30 ng/mL). The final infusion formulation of TILs was in 0.9% sodium chloride with 2.5% human serum albumin, 10% DMSO solution, and 300 IU/mL IL-2 (Fig 1). Conditioning was done with Flu-Cy regimen followed by TILs infusion (Fig 1) followed by IL-2 infusion (600000 IU/kg). Clinical support was provided by Princess Margaret Cancer Centre, Toronto and cell therapy manufacturing was done at Elvina Regenerative, Malaysia. Only two doses of IL-2 post TILs could be completed. Daily IL-6 levels were monitored for CRS (Fig 2). Major complications during treatment are enumerated in Table 1 and Fig 3. Despite best of efforts, she succumbed to the complications on the 9th post infusion day. TILs is an upcoming treatment modality for solid tumors. Proper patient selection is important. Multidisciplinary team that can manage complications affecting virtually any organ is important for performing TILs.