The disclosure relates generally to alpha polyglutamated raltitrexed, formulations containing liposomes filled with alpha polyglutamated raltitrexed, methods of making the alpha polyglutamated raltitrexed and liposome containing formulations, and methods of using polyglutamated alpha polyglutamated raltitrexed and liposome containing formulations to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).