Syllabus

Course Meeting Times

Lectures: 1 session / week, 2 hours / session

Prerequisites

At least one of the following prerequisites is required:

7.03 Genetics

7.05 General Biochemistry

7.06 Cell Biology

7.28 Molecular Biology

Course Description

Almost everyone knows someone whose life has been affected by cancer. This devastating disease, which still carries a social stigma in certain parts of the world, generally remains unbeatable despite numerous efforts to curb and curtail it since the inception of the War on Cancer in the 1970s. Why is cancer such a difficult disease to treat? Despite all the effort and money poured into developing new cancer treatments, why are there so few cancer therapies that specifically target tumor cells? What is the best system to model the development of a human tumor? How can novel therapies be tested in a system that mimics the human body by modeling the interaction between human tumor cells and a human immune system, which plays a role in the detection and elimination of tumor cells? Cancer is thought to develop and spread by escaping surveillance from human immune cells, which would otherwise eliminate it. How can new treatment modalities, especially immune-based therapies that harness the natural ability of immune cells to kill target cells, be developed to treat cancer?

These and other questions will be addressed in this course. We will explore the concepts of mouse models for human cancer, humanized cancer mice and cancer immunotherapy by reading recent and classic research articles. Humanized mice, like Mouse Man from the comic world, are essentially mice on the outside and human in the inside because of the presence of an intact and functional human immune system after engraftment with human stem cells. In humanized cancer mice the development of a human tumor occurs alongside a normal human immune system. We will focus on analyzing and critiquing research papers describing the development of human cancer models using humanized mice, thus hopefully mirroring the situation in patients.

A review of the literature and a dissection of experimental designs will serve as a framework to guide discussions about the strengths and weaknesses of humanized mice (also referred to as humice) in cancer research and their unique position as a platform for the testing of new therapies prior to use in the clinic. The course will end with the exploration of a tantalizing new concept: the development of "personalized mice" or mouse "avatars" for individual cancer patients to test drug toxicities prior to dosing the patient as an effort to improve therapeutic efficacy and minimize undesired side effects. Many believe that immunotherapies represent the future of cancer therapy and humanized mice are a recent addition to the cancer biologist's tool-kit for modeling human cancer.

This course will act as an introduction to the latest developments in the fields of cancer biology and immunotherapy. We will use the humice cancer field as a vehicle to fulfill the primary objective of this course—the art and science of reading, analyzing and critiquing research articles. We will also have the opportunity to attend one or more seminars by experts in the field and visit a research laboratory actively involved in the generation of cancer humice.

Format

This course will be divided into three units. In each weekly session, we will discuss two papers from the primary research literature. Students are expected to read the papers and to formulate one question per paper and submit them to the instructor prior to the class. These questions may address any aspect of the paper and will be discussed at each session. During class, there will be a group discussion of the assigned papers, and students will be selected at random to present figures from the papers. In discussing the papers, emphasis will be placed on evaluating the hypothesis, experimental design and interpretation of results. At the end of each session, the instructor will briefly introduce the papers for the following week. In addition, there will be two assignments, one written and one oral. The written assignment will be due at the beginning of class on Week 7, and the oral presentations will take place during the last class.

Course Objectives

The main objectives of this course are as follows:

1. To introduce students to the primary scientific literature and the process of reading research publications.
2. To expose students to the emerging field of humanized mouse models in the development and testing of novel cancer therapies. Course objectives will be met through class discussions and take-home / in-class assignments.

By the end of the semester students should be able to:

• Read, comprehend, and critically evaluate the primary research literature.
• Understand how to search for primary research articles relevant to the fields of humanized mice and cancer immunotherapy (PubMed, Google Scholar, MIT Library eJournals, etc.).
• Orally present papers from the primary scientific literature and engage in discussions.
• Comprehend techniques used to develop various humanized mouse models.
• Understand the relationship between cancer and the immune system, and the potential of cancer immunotherapy.
• Understand how humanized mouse models or Mouse Avatars can be used to improve cancer chemotherapy regimens and develop new immunotherapies.

Grading

The class is graded on a pass / fail basis for 6 units, and grades will be based on participation in discussion every week, satisfactory completion of the written and oral assignments, and attendance.