Case for Leila
1.Virus Hunters
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Wet lab
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Mouse Models
We are looking for ideas on how to boost her immune system and target this cancer based on its unique genetic profile.
https://transgeneome.mpi-cbg.de/transgeneomics/public/bacFinder.html
Case Summary
Leila is a 37-year-old NYC-based entrepreneur who was diagnosed with vulvar epithelioid sarcoma in March 2019. She underwent two attempted resections and then a radical hemivulvectomy (left) and pelvic lymph node removal, but the tumor kept growing back aggressively. After 6 weeks on the experimental gene therapy drug Tazemetostat, she presented with lung mets in July and was switched to aggressive chemotherapy. The tumors are high-grade and despite shrinking 90% with two rounds of AIM chemo (doxorubicin/ifosfamide), by late summer it spread to a lymph node on her right clavicle and her lungs appeared to have more tumors forming. After switching to two rounds of gemcitabine/docetaxel in September, she developed pneumonitis and bone mets in her ribs and spine, so she did a round of steroids and started a new chemotherapy (liposomal doxorubicin). In November she had targeted radiation on her clavicle lymph node which was pressing painfully on the nerves of her jugular vein, as well as full lung radiation in December to the right lung (the left lung is clear). Also in December, she began immunotherapy (Opdivo) and was given another round of AIM when her lung symptoms became uncontrolled: this appears to have brought the disease back under control. We don’t have much time based on how quickly this is moving and how chemo-resistant it seems to be. We are looking for the best IO/vaccine/experimental options to pursue which can be developed within the next 6 months, the sooner the better. We are exploring vaccines, CRISPR-edited T-cell therapy, HDAC targeting/valproic acid, a GSK-3β inhibitor, other chemo combos, and other IO combos. Leila’s Cancer was sequenced by Memorial Sloan Kettering (MSK) and a German company called Cegat and her primary oncologist is Dr. Mrinal Gounder at MSK and her consulting oncologist is Dr. Michael Castro.
UPDATE: Leila might have a good chance of responding to checkpoint inhibitor immunotherapy because of a specific mutation in her cancer: new research indicates that her SMARCB1 mutation causes endogenous retroviruses to become expressed as antigens. The challenge at the moment is that Leila’s T-cells will be depleted. We are looking for ideas on how to boost her immune system and target this cancer based on its unique genetic profile.
TIMELINE
• March: biopsy after cosmetic resection results in diagnosis of aggressive vulvar proximal-type Epithelioid Sarcoma
• April-May: two attempted resections, including a radical hemivulvectomy (left) and lymph node resection with lymph node transplant. Surgeries do not result in clear margins.
• May-Jun: Treatment with Tazemetostat (Epizyme) initiated (continued for 6 weeks)
• July: lung biopsy confirms metastasis; Leila is taken off Tazemetostat and switched to chemo (AIM = doxorubicin/Ifosfamide)
• August: CT scans show total tumor volume decreases significantly (90%) with two rounds of AIM
• Sep: Leila experiences extreme shoulder pain due to new swollen nodule near jugular vein; lung scans also show a region of opacity that might be malignant pleural effusion. Leila is taken off AIM and initiatives new chemo regime: Gemcitabine/Docetaxel combination
• Oct: minimal to no responsiveness to new chemo, pain and lung symptoms increase, mouse models initiated from lung tumor biopsy
• Early Nov: recurring low-grade fevers results in diagnosis of pneumonitis; fluid builds up in lungs, requiring intrusion of PleurX catheter; bone mets confirmed in vertebrae and ribs. Leila is taken off Gemcitabine/Docetaxel and put on steroids + Liposomal Doxorubicin, multiple rounds of targeted radiation administered on clavicle nodule, max dose of oxygen and fentanyl patch used for pain in the shoulder and lower back/spine
• Dec: Lung symptoms and pain worsen. Leila is taken off Liposomal Doxorubicin and put on Votrient. She then starts her first round of Opdivo and immediately undergoes five rounds of radiation to her right lung where the tumors are growing rapidly. After radiation, her platelet count decreases materially and pain and breathing difficulty is at an all-time high, so she was taken off Votrient and put on another round of AIM which, scans pending, seems to have been very effective.
• Jan: Leila's primary oncologist recommends commencing a second round of AIM in 1-2 weeks (once she has fully recovered from the first round and her blood cell counts are up). They also plan to do another dose of Opdivo as soon as it is safe to do so. Her pain has decreased significantly, her white blood cell counts are starting to increase naturally, and her lung symptoms are much better after the AIM treatment.
**In Progress: mouse modeling has commenced via Champions Oncology (5 mouse lines implanted with cancer cells to test chemo drug combinations - should be ready in 2-3-months)