HUMAN PRACTICES

Introduction

Human Practices is one of the most essential facets of a viable project. It is integral to connect with any person or organization that our project directly or indirectly affects. With this in mind, we tried to interact with people and professionals from different backgrounds that could potentially contribute to our cause.


One of our first exposures to human practices was the BITSAA Global Meet in January 2023, where our team interacted with various alumni from our institute. This was a way of connecting with a large number of people from different ages and working in different sectors, which helped us gather contacts and plan our next moves. We then set up meetings with biotechnology executives, Mr. Kumaril Bhargava and Mr. Anupam Dokeniya, our college alumni, who helped us connect with more people. Slowly we narrowed to talking to more scientifically niche people who could help us with our ideation, as in our meeting with the oncologists at ACTREC. We were lucky to also talk to Melina Soares, from Immuneel Therapeutics Private Limited, one of the only companies in India working on CAR T cell therapy. These meetings helped us ideate a scientifically sound concept. Once we finalized our idea, we spoke to Dr. Shekhar Salkar, one of our state’s senior most oncologists, we talked about our hypothesis but also about its implementation in India. Through Dr. Salkar, we also managed to get in touch with patients, to gauge their needs and concerns with respect to our treatment


We believe that human practices start from our community, and studying in such a large university, we have a large platform to address. We engaged with our students at an orientation event where we introduced iGEM BITS Goa as a club, and spoke about our goals and activities. We were interviewed by our university's journalism department, where we spoke about our project, and how we as a club are trying to create an overall paradigm shift in our university culture to bring more people to our cause. We are also working in collaboration with our university’s NGO, to get in touch with underprivileged people who we could potentially help.

Interviews

  • Interview with Dr. Shekhar Salkar
    We managed to get in touch with Dr. Shekhar Salkar, one of the topmost senior oncologists in our state, Goa. Dr. Salkar is the Ex-Chairman of Goa Medical Council, and currently works as a senior oncologist at Manipal Hospital, Goa. We were also joined by Dr. Mahadeva Swamy, a Hematologic Oncologist working in the same hospital. We commenced the meeting with us explaining our project idea and the science behind it. They asked us about our experimental procedures and how we are planning to show our proof of concept. The agenda of this meeting was to ask about hurdles and issues this therapy will face during real-world implementation.

    Health Concerns associated with CAR T therapy

    First, we asked about the potential side-effects of such a therapy, to which the doctors said they know in theory that it could lead to cytokine release syndrome or leukoencephalopathy, but a more comprehensive answer could be generated only after a clinical trial.

    CAR T cell therapy in India - hurdles to overcome

    The main focus of this meeting was to ask about the logistics and cost efficacy of CAR-T cell therapy. Both the doctors agreed that one of the major issues with CAR T-cell therapy is the fact that it is not affordable for the masses, especially in a country like India with a significant number of people below the poverty line. This is also a major reason why there are not many clinical trials of CAR T-cell therapies in India. They explained that a very significant cost reduction is needed to fund such clinical trials on a larger scale.

    Patient response to CAR T cell therapy

    To see whether a real world implementation of our idea is possible, we also need to take into consideration the psyche of the patients. Since doctors work in close contact with patients, we asked questions about how a novel therapy like this one is introduced to the patient, and how receptive they will be to such a therapy. Dr. Swamy responded by saying that patients are mostly not reluctant in the case of a clinical trial as it is free of cost for them, as well as giving them a chance to be cured, but again the major hurdle faced is the cost of clinical trials. The doctors also said that CAR T-cell therapy needs some impetus, especially towards solid tumors, so STAT3 is being looked at by various pharmaceutical companies and by academia as a potential target. Lastly, to increase our reach to the grassroot level, we enquired whether we could send out a completely anonymous questionnaire to some cancer patients so we can have a more complete study and learn the opinions of patients who, at the end of the day will be the end users of our idea.

  • Interview with Tata Memorial Hospital’s Advanced Center for Treatment, Research and Education in Cancer(ACTREC)
    By January 2023, after a 3 month long ideation stage where we did extensive literature review and brainstorming, we had a rudimentary idea of what our project was going to be. Now, it was time to consult professionals and clinicians working in the field of cancer treatment to validate and improve upon our ideas and hypotheses.

    We reached out to thoracic oncologists from the prestigious Tata Memorial Hospital’s Advanced Center for Treatment, Research and Education in Cancer(ACTREC) - Dr. Vanita Noronha, Dr. Kumar Prabhash and Dr. Maheema Bhaskar who lent us their valuable insights regarding the feasibility and implementation of our idea.

    VEGFR as a Small Molecule Drug Target

    In the initial stages, our project design consisted of a ‘docking’ and a ‘blocking’ element. The docking element would serve the purpose of detecting the tumor microenvironment based on certain parameters - low pH, hypoxia and an increased expression of VEGFR in tumor cells. The panel pointed out that since VEGFR is not a very specific marker for tumors, drugs targeting this receptor have not been very successful as of yet. While small molecule inhibitors against targets such as the RET receptor are also used in therapy, small molecule VEGFR inhibitors have not been very successful. VEGFR is also significantly expressed in non-cancerous cells. While TKIs have been fairly successful against some receptors, they have not worked very well for VEGFR. VEGFR was therefore ruled out for being a not very safe or effective target and our model was revised to exclude it.

    Effective Delivery of Small Molecule Drugs

    Drugs which are used for the treatment of cancer are often toxic to healthy cells as well which makes efficient and specific drug delivery a key aspect of developing a treatment for a particular type of cancer. Small molecule drugs have either proven to be very effective or very toxic, and often - both. Therefore, it is important to tread carefully in this regard. Dr. Kumar introduced us to the idea of loading a drug onto an antibody attached to a linker such that it is released at the local area. This technique has been reasonably successful. A variation of this concept was incorporated into our project where we would load honokiol(STAT3 inhibitor) onto the CBR receptor expressed on the T-cell. It would be transported along with the T-cell and released at the location of the tumor.

    CAR T-cell therapy in the Indian Context

    We discussed the current stages of development of CAR T-cell therapy in the Indian context and the future prospects in this regard. They confirmed that so far, there has not been significant progress in developing CAR T therapy which is effective for solid tumors which our team is attempting to accomplish through this project.

    From the technology perspective, CAR T therapy is very complex and challenging. Efficacy wise it is quite modest and has proven to be effective only for a few types of leukemias and lymphomas as they are liquid tumors. In general, CAR T or CAR NK therapy is not very widely available or researched upon in India. Checkpoint inhibition has also made a significant impact in cancer immunotherapy. However, there remains a massive unmet need for better cancer therapies.

    Through our discussion with the ACTREC panel, we gained a lot of useful insights which helped us revise and improve our project. We implemented their advice in our project towards developing a safe and effective treatment of NSCLC.

  • Interview with Kumaril Bhargava and Anupam Dokeniya
    Our institute is known for its extensive and extremely helpful alumni network, so one of our first meetings was set up with two other alumni from BITS, Kumaril Bhargava and Anupam Dokeniya who are biotechnology executives. We thought that this would be a good starting point as we could ask them for not only advice on our project, but also get in touch with more people that could benefit us.

    CAR T cell therapy as an upcoming treatment

    Our project involves using CAR T cell therapy for the treatment of solid tumors, so we started with a discussion about the most recent developments in CAR T cell therapy. We asked Mr. Bhargava and Mr. Dokeniya whether CAR T cell therapy can be developed further. They talked about how this therapy is being looked at by more pharmaceutical companies each day, and quite a few clinical trials are up incoming in China, United States and some areas in Europe. However, they did mention that the growth of CAR T cell therapy in India is difficult because a large amount of capital must be invested in it and we do not have the infrastructure for that in our country.

    Developing a better model to existing CAR T therapies

    We explained our project, as well as our whole mechanism to them - one of our initial iterations of the concept involved attaching a new domain to the Chimeric Antigen receptor, on which we would attach a prodrug that would cleave at the tumor site with the help of an enzyme secreted by the T cell itself. We spoke about our basic plan of showing this proof of concept - involving basic wet lab experiments as well as in silico modeling for the components that we do not have the lab facilities for. Although they are not experts in the field, they assured us that our hypothesis was sound, and gave us a lot of helpful general advice.

    They told us to make sure to do a comprehensive literature review and focus on finding gaps to fill. Mr. Bhargava spoke about 4 of the most important aspects that we should take into consideration when developing our idea - efficacy, safety, convenience and dosing. This was very helpful advice, and in the next iteration of our idea we made sure to cover all these points.

    Target specific efficient delivery of enzyme

    One of the major concerns we had with our proposal was the increase in metabolic load on the cell as we were not only attaching a new domain to the receptor but also synthesizing the enzyme. Mr. Bhargava validated our concern and provided suggestions for alternatives. He spoke about Thermally Activated Liposomes, nanocarriers and nanovesicles for a more specific treatment. We implemented this suggestion in our next version of the project which uses a biocompatible nanocarrier - based delivery system, which is highly specific to the tumor in question, to deliver our antagonist.

    They also spoke about people they knew that could help us, from scientists, to other alumni from our college, to more biotechnology industrialists for not only research help but also for fundraising. We were pleased by their interest in knowing more about the competition, as well as their initiative for helping us in multiple ways. Mr. Dokeniya suggested that we should spread awareness about our project at the BITSAA Global Meet, which we did and received a lot of help from our alumni.

  • Interview with Immuneel Therapeutics Private Limited
    We had the opportunity to set up a meeting with Melina Soares, Head of Innovation and Intellectual at Immuneel Therapeutics Private Limited, one of the only companies in India working on CAR T cell therapy.

    The meeting started with us discussing the basics of our project - what cancer we are working on and why. We elaborated on our reasoning behind selecting NSCLC, and working on CAR T cell therapy. We received some valuable starting tips from her, as well as experimental ideas. What made this meeting extremely helpful was that Melina initiated as well as encouraged brainstorming along with us. She gave valuable tips on a lot of aspects of our project which we could explore, such as using an organ culture to study the tumor microenvironment or using biodegradable sutures as a delivery mechanism. The tremendous amount of ideas and suggestions that she provided us with proved to be very helpful in our thinking and ideation of our project concept. We decided to incorporate the use of biodegradable microsutures as a potential mechanism of delivering our antagonist - AM6538. We then explained to her the mechanism of drug release in our concept, to which she expressed her concerns, but gave us advice on how to test it experimentally. We were grateful to get in contact with someone directly working with CAR T cells, as this meeting really helped us in understanding not just the mechanism of cancer therapies, but also CAR T cell therapy in particular, which was integral to our project.

BGM

The BITSAA Global Meet - 2023 was a grand conference that attracted a multitude of our esteemed alumni from our university, spread across continents. This year it was held in the city of Jaipur, and three members of our team travelled to attend this event. Our motive for participating in this event was clear - to enlighten our own alumni about Project CARkinos and its potential impact, and to amplify our collective efforts in the fight against lung cancers.

The event served as an ideal platform for our outreach, as we successfully managed to educate and spark some meaningful discussions with our alumni, facilitating them to convey the knowledge further with their network. We boosted our presence through various media like merchandise, posters, and brochures that summarised our pitch.

Through the end of this three-day event, we managed to not only inform but also inspire almost every one of the 1500+ attendees present, including some of our C-suite alumni from Fortune 100 and 500 companies. As a team, this event helped us craft our one-minute pitch - and enabled us to reach out to a lot more individuals further in time. We also managed to get monetary pledges and get contacts of some high-profile individuals, which have proven to be pivotal for our project’s success. BGM proved to be a success in various ways - we obtained a significant amount of our funding from the alumni we interacted with during the conference, and got in touch with people from various different sectors and industries that could help with research and scientific expertise as well. Talking about our project to a generalised audience helped us gain perspective that we would not get if we catered to a niche sample space.

Orientation

On September 10th, we hosted an orientation session for the incoming freshmen of the 2023 batch at BITS Goa. Our main objective was to introduce our team, as well as talk about iGEM BITS Goa as a club of highly motivated students with diverse backgrounds with the goal of solving a global problem with the help of synthetic biology.

During the session, we delved into the intricacies of synthetic biology, highlighting its real-world applications. We also provided insights into our ongoing project, which involves modifying CAR T therapy to combat NSCLC, a form of lung cancer.

The response from the students, from freshmen to juniors was remarkable. They showed a keen interest in delving deeper into the world of synthetic biology and its potential. We introduced our team members individually, showcasing their roles and contributions within the club. This personal touch helped students connect with our mission and vision and further piqued the curiosity of the first-year students, motivating them to explore the fascinating world of synthetic biology, no matter what their majors are.

The enthusiasm displayed by the freshmen after the presentation was a clear indicator of their eagerness to become part of our journey, and we certainly hope to see them in our team next year!

DoJMA

Department of Journalism and Media Affairs (DoJMA), is BITS Pilani Goa’s official and longest running news department. Their newsletter is viewed across multiple colleges in India making them one of the biggest representatives of BITS Goa to the outside world. They had interviewed multiple technical clubs of the institute in the past month. These interviews were an effort to showcase the ideals of the club alongside with broadcasting the work and events that they are putting out. iGEM BITS Goa, amongst all technical clubs, is the only club representing the field of Biology in general, let alone Genetic Engineering and Life Sciences. They asked about the multiple workshops we hold throughout the year, ranging from simple and fun agar art workshops to full-fledged town hall-style debates on bioethics and the morals of genetic engineering.

They even asked us about our foundation and the principles that we promote. One of our core principles that is prevalent in every one of our events has to be the ethical and sustainable approach to Genetic Engineering and its many uses. We mentioned how we hold various talks across campus to promote this idea and also get students from multiple branches of college to be interested in Bioengineering. They concluded their questions with how we move forward with our projects and how as a student run club, we keep ourselves dynamic as the world of genetic engineering keeps changing around us. In a university that primarily focuses on traditional engineering disciplines and allied fields, our club’s aim is to go beyond the mould of iGEM – where we seek to promote the overall ideology of how a multi-disciplinary approach to Biology could revolutionize all the research being performed, as Biology is naturally meant and designed to be looked at from different vantage points. This interview really helped us promote iGEM BITS Goa as a club, and we received an overwhelming response from students who wanted to know more about us and what we do.

Nirmaan

We collaborated with an on-campus chapter of the pan India NGO - Nirmaan, which focuses on public health as one of their core areas. As October is the International Breast Cancer Awareness month, we conducted a breast self-examination workshop for all women on campus. This included women from the housekeeping staff, cafeteria workers, etc., who are all from extremely marginalized communities with little to no access to any form of healthcare facilities. The workshop also involved a segment where we talked about possible measures of early detection of lung cancer which include yearly chest exams and X - Rays, apart from something known as a low-dose CT (LDCT) scan, which can detect abnormal areas in the chest cavity (which may be cancer) much more accurately. Symptoms of lung cancer were discussed and measures to avoid the occurrence of it were also discussed. The focus group for the lung cancer workshop was mostly older men (> 40 years of age) - which included mess/dining hall workers, housekeeping staff, hostel assistants etc., who were vulnerable to the primary cause of lung cancer i.e. smoke in any form.

The focus of both workshops was to make healthcare accessible to people from all strata, regardless of financial status. Both Breast and Lung Cancers are one of the leading causes of death in India and both can be largely avoided if proper precautions are taken, but marginalized communities often have disproportionate access to such resources causing a disproportionate rise in the number of cases and fatalities from these communities.